USMLE Step 1 2026 Practice Exam | High-Yield
Questions with Verified Answers & Rationales |
INSTANT PDF DOWNLOAD
Welcome to this high-yield USMLE Step 1 practice exam. This resource contains 200 questions covering
pathology, pharmacology, physiology, microbiology, biochemistry, immunology, behavioral science, and
genetics. Each question mirrors the style and difficulty of the actual Step 1. Every answer includes a clear
rationale. Use this exam to identify weak areas and build confidence.
Key Topics Covered
➢ General Pathology – Inflammation, neoplasia, hemodynamics, genetics
➢ Organ Systems – Cardiovascular, respiratory, renal, GI, endocrine, reproductive, musculoskeletal,
neurology
➢ Pharmacology – Mechanisms, side effects, autonomic, cardiovascular, antimicrobials
➢ Microbiology & Immunology – Bacteria, viruses, fungi, parasites, hypersensitivity, autoimmunity
➢ Biochemistry & Molecular Biology – Metabolism, enzymes, nutrition, cell biology
➢ Physiology – Acid-base, endocrine, cardiac, respiratory, renal
➢ Behavioral Science & Biostatistics – Study designs, bias, ethics, epidemiology
Questions 1–200
1. A 55-year-old male with a history of hypertension presents with acute onset of severe substernal
chest pain radiating to the left arm. ECG shows ST elevation in leads V1-V4. Which coronary artery is
most likely occluded?
A) Left anterior descending artery
B) Right coronary artery
C) Left circumflex artery
D) Posterior descending artery
Answer A: Left anterior descending artery
Rationale: LAD occlusion causes anteroseptal STEMI (V1-V4). RCA causes inferior (II, III, aVF). LCx causes
lateral (I, aVL, V5-V6).
,2. A 30-year-old woman presents with fatigue, proximal muscle weakness, and a heliotrope rash.
Which autoantibody is most specific for dermatomyositis?
A) Anti-Jo-1
B) Anti-Mi-2
C) Anti-Scl-70
D) Anti-Sm
Answer B: Anti-Mi-2
Rationale: Anti-Mi-2 is highly specific for dermatomyositis. Anti-Jo-1 is associated with antisynthetase
syndrome (interstitial lung disease).
3. A 67-year-old man with a 50-pack-year smoking history presents with hemoptysis and weight loss.
Chest CT shows a 4 cm right hilar mass. Biopsy reveals squamous cell carcinoma. Which
paraneoplastic syndrome is most commonly associated with this tumor?
A) Hypercalcemia
B) Syndrome of inappropriate antidiuretic hormone (SIADH)
C) Lambert-Eaton syndrome
D) Hypertrophic osteoarthropathy
Answer A: Hypercalcemia
Rationale: Squamous cell lung cancer often secretes PTH-related peptide causing hypercalcemia. SIADH is
more common in small cell lung cancer.
4. A 22-year-old male has a seizure after staying up all night studying. He has no previous history.
Which finding on EEG would be most suggestive of juvenile myoclonic epilepsy?
A) Generalized spike-and-wave discharges at 3-6 Hz
B) Focal temporal spikes
C) Hypsarrhythmia
D) Triphasic waves
Answer A: Generalized spike-and-wave discharges at 3-6 Hz
Rationale: Juvenile myoclonic epilepsy shows generalized spike-and-wave (often 4-6 Hz) provoked by sleep
deprivation. Myoclonic jerks occur after awakening.
5. A 45-year-old female presents with episodic flushing, diarrhea, and wheezing. Urine 5-HIAA is
elevated. Which tumor is most likely?
,A) Gastrinoma
B) VIPoma
C) Carcinoid tumor
D) Glucagonoma
Answer C: Carcinoid tumor
Rationale: Carcinoid syndrome (flushing, diarrhea, bronchospasm) from serotonin secretion; 5-HIAA is
diagnostic. Midgut carcinoids are classic.
6. A 68-year-old male with atrial fibrillation on warfarin presents with acute onset of right arm
weakness and aphasia. INR is 1.2. Non-contrast head CT is normal. Which is the most appropriate
next step?
A) Administer IV tissue plasminogen activator (tPA)
B) Start heparin infusion
C) Repeat CT in 6 hours
D) Aspirin 325 mg
Answer A: Administer IV tissue plasminogen activator (tPA)
Rationale: Acute ischemic stroke within 3-4.5 hours with normal CT and INR <1.4 qualifies for tPA. Do not
delay for repeat imaging.
7. A 32-year-old pregnant woman at 28 weeks gestation presents with new-onset hypertension (BP
160/100) and proteinuria (3+). She has no headache or visual changes. Which diagnosis is most
appropriate?
A) Gestational hypertension
B) Preeclampsia without severe features
C) Chronic hypertension
D) HELLP syndrome
Answer B: Preeclampsia without severe features
Rationale: New hypertension after 20 weeks with proteinuria defines preeclampsia. Severe features include
BP ≥160/110, thrombocytopenia, or end-organ dysfunction.
8. A 55-year-old male with alcohol use disorder presents with confusion, ataxia, and
ophthalmoplegia. Which vitamin deficiency is responsible?
A) Thiamine (B1)
, B) Niacin (B3)
C) Vitamin B12
D) Pyridoxine (B6)
Answer A: Thiamine (B1)
Rationale: Wernicke’s encephalopathy (confusion, ataxia, ophthalmoplegia) is caused by thiamine
deficiency. Give IV thiamine before glucose.
9. A 28-year-old male presents with a painless, non-pruritic ulcer on his penis. Darkfield microscopy
reveals spirochetes. Which serologic test becomes positive first?
A) Rapid plasma reagin (RPR)
B) Fluorescent treponemal antibody absorption (FTA-ABS)
C) Treponema pallidum particle agglutination (TP-PA)
D) Venereal Disease Research Laboratory (VDRL)
Answer B: Fluorescent treponemal antibody absorption (FTA-ABS)
Rationale: Treponemal tests (FTA-ABS, TP-PA) become positive earlier than non-treponemal tests (RPR,
VDRL), usually within 2-3 weeks of chancre.
10. A 62-year-old female with rheumatoid arthritis presents with a non-healing ulcer on her lower
leg. She has palpable purpura. Which extra-articular manifestation is most likely?
A) Rheumatoid vasculitis
B) Pyoderma gangrenosum
C) Necrobiosis lipoidica
D) Venous stasis ulcer
Answer A: Rheumatoid vasculitis
Rationale: Palpable purpura and leg ulcers in RA suggest small-vessel vasculitis (immune complex
deposition). Biopsy shows leukocytoclastic vasculitis.
11. A 45-year-old male presents with acute, severe, colicky right flank pain radiating to the groin,
nausea, and hematuria. Non-contrast CT shows a 5 mm stone at the left ureterovesical junction.
Which management is most appropriate?
A) Medical expulsive therapy with tamsulosin and hydration
B) Extracorporeal shock wave lithotripsy (ESWL)
C) Ureteroscopy with laser lithotripsy
Questions with Verified Answers & Rationales |
INSTANT PDF DOWNLOAD
Welcome to this high-yield USMLE Step 1 practice exam. This resource contains 200 questions covering
pathology, pharmacology, physiology, microbiology, biochemistry, immunology, behavioral science, and
genetics. Each question mirrors the style and difficulty of the actual Step 1. Every answer includes a clear
rationale. Use this exam to identify weak areas and build confidence.
Key Topics Covered
➢ General Pathology – Inflammation, neoplasia, hemodynamics, genetics
➢ Organ Systems – Cardiovascular, respiratory, renal, GI, endocrine, reproductive, musculoskeletal,
neurology
➢ Pharmacology – Mechanisms, side effects, autonomic, cardiovascular, antimicrobials
➢ Microbiology & Immunology – Bacteria, viruses, fungi, parasites, hypersensitivity, autoimmunity
➢ Biochemistry & Molecular Biology – Metabolism, enzymes, nutrition, cell biology
➢ Physiology – Acid-base, endocrine, cardiac, respiratory, renal
➢ Behavioral Science & Biostatistics – Study designs, bias, ethics, epidemiology
Questions 1–200
1. A 55-year-old male with a history of hypertension presents with acute onset of severe substernal
chest pain radiating to the left arm. ECG shows ST elevation in leads V1-V4. Which coronary artery is
most likely occluded?
A) Left anterior descending artery
B) Right coronary artery
C) Left circumflex artery
D) Posterior descending artery
Answer A: Left anterior descending artery
Rationale: LAD occlusion causes anteroseptal STEMI (V1-V4). RCA causes inferior (II, III, aVF). LCx causes
lateral (I, aVL, V5-V6).
,2. A 30-year-old woman presents with fatigue, proximal muscle weakness, and a heliotrope rash.
Which autoantibody is most specific for dermatomyositis?
A) Anti-Jo-1
B) Anti-Mi-2
C) Anti-Scl-70
D) Anti-Sm
Answer B: Anti-Mi-2
Rationale: Anti-Mi-2 is highly specific for dermatomyositis. Anti-Jo-1 is associated with antisynthetase
syndrome (interstitial lung disease).
3. A 67-year-old man with a 50-pack-year smoking history presents with hemoptysis and weight loss.
Chest CT shows a 4 cm right hilar mass. Biopsy reveals squamous cell carcinoma. Which
paraneoplastic syndrome is most commonly associated with this tumor?
A) Hypercalcemia
B) Syndrome of inappropriate antidiuretic hormone (SIADH)
C) Lambert-Eaton syndrome
D) Hypertrophic osteoarthropathy
Answer A: Hypercalcemia
Rationale: Squamous cell lung cancer often secretes PTH-related peptide causing hypercalcemia. SIADH is
more common in small cell lung cancer.
4. A 22-year-old male has a seizure after staying up all night studying. He has no previous history.
Which finding on EEG would be most suggestive of juvenile myoclonic epilepsy?
A) Generalized spike-and-wave discharges at 3-6 Hz
B) Focal temporal spikes
C) Hypsarrhythmia
D) Triphasic waves
Answer A: Generalized spike-and-wave discharges at 3-6 Hz
Rationale: Juvenile myoclonic epilepsy shows generalized spike-and-wave (often 4-6 Hz) provoked by sleep
deprivation. Myoclonic jerks occur after awakening.
5. A 45-year-old female presents with episodic flushing, diarrhea, and wheezing. Urine 5-HIAA is
elevated. Which tumor is most likely?
,A) Gastrinoma
B) VIPoma
C) Carcinoid tumor
D) Glucagonoma
Answer C: Carcinoid tumor
Rationale: Carcinoid syndrome (flushing, diarrhea, bronchospasm) from serotonin secretion; 5-HIAA is
diagnostic. Midgut carcinoids are classic.
6. A 68-year-old male with atrial fibrillation on warfarin presents with acute onset of right arm
weakness and aphasia. INR is 1.2. Non-contrast head CT is normal. Which is the most appropriate
next step?
A) Administer IV tissue plasminogen activator (tPA)
B) Start heparin infusion
C) Repeat CT in 6 hours
D) Aspirin 325 mg
Answer A: Administer IV tissue plasminogen activator (tPA)
Rationale: Acute ischemic stroke within 3-4.5 hours with normal CT and INR <1.4 qualifies for tPA. Do not
delay for repeat imaging.
7. A 32-year-old pregnant woman at 28 weeks gestation presents with new-onset hypertension (BP
160/100) and proteinuria (3+). She has no headache or visual changes. Which diagnosis is most
appropriate?
A) Gestational hypertension
B) Preeclampsia without severe features
C) Chronic hypertension
D) HELLP syndrome
Answer B: Preeclampsia without severe features
Rationale: New hypertension after 20 weeks with proteinuria defines preeclampsia. Severe features include
BP ≥160/110, thrombocytopenia, or end-organ dysfunction.
8. A 55-year-old male with alcohol use disorder presents with confusion, ataxia, and
ophthalmoplegia. Which vitamin deficiency is responsible?
A) Thiamine (B1)
, B) Niacin (B3)
C) Vitamin B12
D) Pyridoxine (B6)
Answer A: Thiamine (B1)
Rationale: Wernicke’s encephalopathy (confusion, ataxia, ophthalmoplegia) is caused by thiamine
deficiency. Give IV thiamine before glucose.
9. A 28-year-old male presents with a painless, non-pruritic ulcer on his penis. Darkfield microscopy
reveals spirochetes. Which serologic test becomes positive first?
A) Rapid plasma reagin (RPR)
B) Fluorescent treponemal antibody absorption (FTA-ABS)
C) Treponema pallidum particle agglutination (TP-PA)
D) Venereal Disease Research Laboratory (VDRL)
Answer B: Fluorescent treponemal antibody absorption (FTA-ABS)
Rationale: Treponemal tests (FTA-ABS, TP-PA) become positive earlier than non-treponemal tests (RPR,
VDRL), usually within 2-3 weeks of chancre.
10. A 62-year-old female with rheumatoid arthritis presents with a non-healing ulcer on her lower
leg. She has palpable purpura. Which extra-articular manifestation is most likely?
A) Rheumatoid vasculitis
B) Pyoderma gangrenosum
C) Necrobiosis lipoidica
D) Venous stasis ulcer
Answer A: Rheumatoid vasculitis
Rationale: Palpable purpura and leg ulcers in RA suggest small-vessel vasculitis (immune complex
deposition). Biopsy shows leukocytoclastic vasculitis.
11. A 45-year-old male presents with acute, severe, colicky right flank pain radiating to the groin,
nausea, and hematuria. Non-contrast CT shows a 5 mm stone at the left ureterovesical junction.
Which management is most appropriate?
A) Medical expulsive therapy with tamsulosin and hydration
B) Extracorporeal shock wave lithotripsy (ESWL)
C) Ureteroscopy with laser lithotripsy
