Original COMLEX Level 2–Style Practice
Questions and answers with rationales
A comprehensive collection of original COMLEX Level 2–style practice questions designed to
enhance clinical reasoning, diagnostic skills, and exam preparation across major medical
disciplines, including medicine, surgery, pediatrics, OB/GYN, OMM, ethics, and biostatistics.
Question 1
A 64-year-old man presents with fatigue, weight loss, and increasing abdominal fullness. Physical
examination reveals splenomegaly. CBC shows elevated white blood cells with increased
granulocytes. A genetic test detects the Philadelphia chromosome.
A. Acute lymphoblastic leukemia
B. Chronic myeloid leukemia
C. Chronic lymphocytic leukemia
D. Multiple myeloma
Answer: B. Chronic myeloid leukemia
Explanation: The Philadelphia chromosome results from a t(9;22) translocation producing the BCR-
ABL tyrosine kinase, which is characteristic of chronic myeloid leukemia.
Question 2
A 58-year-old woman presents with progressive fatigue and weakness. Laboratory testing shows
elevated AST and ALT with positive anti-smooth muscle antibodies.
A. Viral hepatitis
B. Autoimmune hepatitis
C. Primary biliary cholangitis
D. Alcoholic hepatitis
Answer: B. Autoimmune hepatitis
Explanation: Autoimmune hepatitis commonly affects women and is associated with anti-smooth
muscle antibodies and elevated transaminases.
Question 3
A 72-year-old man presents with difficulty initiating urination, weak urinary stream, and nocturia.
Digital rectal examination reveals a smooth enlarged prostate.
A. Prostate cancer
B. Benign prostatic hyperplasia
C. Acute prostatitis
D. Bladder carcinoma
Answer: B. Benign prostatic hyperplasia
,Explanation: Smooth enlargement of the prostate causing lower urinary tract symptoms is typical of
BPH.
Question 4
A 26-year-old woman presents with sudden onset unilateral pelvic pain and vaginal bleeding.
Pregnancy test is positive. Ultrasound shows no intrauterine pregnancy.
A. Threatened abortion
B. Ectopic pregnancy
C. Placental abruption
D. Ovarian cyst rupture
Answer: B. Ectopic pregnancy
Explanation: Positive pregnancy test with pelvic pain and absence of an intrauterine pregnancy
should raise concern for ectopic pregnancy.
Question 5
A 35-year-old man presents with severe headache, fever, neck stiffness, and photophobia. Lumbar
puncture shows elevated neutrophils and decreased glucose.
A. Viral meningitis
B. Bacterial meningitis
C. Migraine
D. Subarachnoid hemorrhage
Answer: B. Bacterial meningitis
Explanation: Neutrophilic CSF pleocytosis and low glucose indicate bacterial infection.
Question 6
A 40-year-old woman presents with episodes of palpitations, sweating, and anxiety. Blood pressure is
210/110 mm Hg during episodes. Plasma metanephrines are elevated.
A. Panic disorder
B. Hyperthyroidism
C. Pheochromocytoma
D. Primary hypertension
Answer: C. Pheochromocytoma
Explanation: Episodic hypertension with headaches, diaphoresis, and palpitations suggests
catecholamine excess from pheochromocytoma.
Question 7
,A 60-year-old man develops sudden weakness of the right side of his body. MRI reveals an ischemic
lesion in the left hemisphere.
A. Right MCA stroke
B. Left MCA stroke
C. Right cerebellar stroke
D. Left occipital stroke
Answer: B. Left MCA stroke
Explanation: A left middle cerebral artery infarct causes right-sided weakness and may affect
language centers.
Question 8
A 4-year-old child presents with fever, drooling, muffled voice, and tripod positioning.
A. Croup
B. Epiglottitis
C. Asthma
D. Bronchiolitis
Answer: B. Epiglottitis
Explanation: Drooling, toxic appearance, and tripod positioning indicate epiglottitis, requiring urgent
airway management.
Question 9
A 55-year-old woman presents with fatigue and bone pain. Laboratory testing shows elevated
calcium and total protein. Serum electrophoresis demonstrates a monoclonal spike.
A. Leukemia
B. Multiple myeloma
C. Lymphoma
D. Iron deficiency anemia
Answer: B. Multiple myeloma
Explanation: Multiple myeloma causes monoclonal gammopathy, hypercalcemia, bone pain, renal
dysfunction, and anemia.
Question 10
A 30-year-old man presents with diarrhea, abdominal pain, and weight loss. Colonoscopy reveals
transmural inflammation and skip lesions.
A. Ulcerative colitis
B. Crohn disease
, C. Irritable bowel syndrome
D. Diverticulitis
Answer: B. Crohn disease
Explanation: Skip lesions and transmural inflammation are characteristic of Crohn disease.
Question 11
A 68-year-old woman presents with sudden vision loss and a curtain-like shadow across her visual
field.
A. Cataract
B. Retinal detachment
C. Glaucoma
D. Macular degeneration
Answer: B. Retinal detachment
Explanation: Sudden painless vision loss with a curtain-like visual defect suggests retinal
detachment.
Question 12
A 50-year-old man develops severe chest pain after cocaine use. ECG shows ST-segment elevation.
A. Coronary vasospasm causing myocardial infarction
B. Pericarditis
C. Aortic stenosis
D. Pulmonary fibrosis
Answer: A. Coronary vasospasm causing myocardial infarction
Explanation: Cocaine stimulates sympathetic activity causing coronary vasoconstriction and
increased myocardial oxygen demand.
Question 13
A 7-year-old boy has recurrent infections with encapsulated organisms. Laboratory studies show
absent B cells.
A. T-cell deficiency
B. B-cell deficiency
C. Complement deficiency
D. Neutrophil dysfunction
Answer: B. B-cell deficiency
Explanation: B-cell deficiencies impair antibody production and increase susceptibility to
encapsulated bacterial infections.
Questions and answers with rationales
A comprehensive collection of original COMLEX Level 2–style practice questions designed to
enhance clinical reasoning, diagnostic skills, and exam preparation across major medical
disciplines, including medicine, surgery, pediatrics, OB/GYN, OMM, ethics, and biostatistics.
Question 1
A 64-year-old man presents with fatigue, weight loss, and increasing abdominal fullness. Physical
examination reveals splenomegaly. CBC shows elevated white blood cells with increased
granulocytes. A genetic test detects the Philadelphia chromosome.
A. Acute lymphoblastic leukemia
B. Chronic myeloid leukemia
C. Chronic lymphocytic leukemia
D. Multiple myeloma
Answer: B. Chronic myeloid leukemia
Explanation: The Philadelphia chromosome results from a t(9;22) translocation producing the BCR-
ABL tyrosine kinase, which is characteristic of chronic myeloid leukemia.
Question 2
A 58-year-old woman presents with progressive fatigue and weakness. Laboratory testing shows
elevated AST and ALT with positive anti-smooth muscle antibodies.
A. Viral hepatitis
B. Autoimmune hepatitis
C. Primary biliary cholangitis
D. Alcoholic hepatitis
Answer: B. Autoimmune hepatitis
Explanation: Autoimmune hepatitis commonly affects women and is associated with anti-smooth
muscle antibodies and elevated transaminases.
Question 3
A 72-year-old man presents with difficulty initiating urination, weak urinary stream, and nocturia.
Digital rectal examination reveals a smooth enlarged prostate.
A. Prostate cancer
B. Benign prostatic hyperplasia
C. Acute prostatitis
D. Bladder carcinoma
Answer: B. Benign prostatic hyperplasia
,Explanation: Smooth enlargement of the prostate causing lower urinary tract symptoms is typical of
BPH.
Question 4
A 26-year-old woman presents with sudden onset unilateral pelvic pain and vaginal bleeding.
Pregnancy test is positive. Ultrasound shows no intrauterine pregnancy.
A. Threatened abortion
B. Ectopic pregnancy
C. Placental abruption
D. Ovarian cyst rupture
Answer: B. Ectopic pregnancy
Explanation: Positive pregnancy test with pelvic pain and absence of an intrauterine pregnancy
should raise concern for ectopic pregnancy.
Question 5
A 35-year-old man presents with severe headache, fever, neck stiffness, and photophobia. Lumbar
puncture shows elevated neutrophils and decreased glucose.
A. Viral meningitis
B. Bacterial meningitis
C. Migraine
D. Subarachnoid hemorrhage
Answer: B. Bacterial meningitis
Explanation: Neutrophilic CSF pleocytosis and low glucose indicate bacterial infection.
Question 6
A 40-year-old woman presents with episodes of palpitations, sweating, and anxiety. Blood pressure is
210/110 mm Hg during episodes. Plasma metanephrines are elevated.
A. Panic disorder
B. Hyperthyroidism
C. Pheochromocytoma
D. Primary hypertension
Answer: C. Pheochromocytoma
Explanation: Episodic hypertension with headaches, diaphoresis, and palpitations suggests
catecholamine excess from pheochromocytoma.
Question 7
,A 60-year-old man develops sudden weakness of the right side of his body. MRI reveals an ischemic
lesion in the left hemisphere.
A. Right MCA stroke
B. Left MCA stroke
C. Right cerebellar stroke
D. Left occipital stroke
Answer: B. Left MCA stroke
Explanation: A left middle cerebral artery infarct causes right-sided weakness and may affect
language centers.
Question 8
A 4-year-old child presents with fever, drooling, muffled voice, and tripod positioning.
A. Croup
B. Epiglottitis
C. Asthma
D. Bronchiolitis
Answer: B. Epiglottitis
Explanation: Drooling, toxic appearance, and tripod positioning indicate epiglottitis, requiring urgent
airway management.
Question 9
A 55-year-old woman presents with fatigue and bone pain. Laboratory testing shows elevated
calcium and total protein. Serum electrophoresis demonstrates a monoclonal spike.
A. Leukemia
B. Multiple myeloma
C. Lymphoma
D. Iron deficiency anemia
Answer: B. Multiple myeloma
Explanation: Multiple myeloma causes monoclonal gammopathy, hypercalcemia, bone pain, renal
dysfunction, and anemia.
Question 10
A 30-year-old man presents with diarrhea, abdominal pain, and weight loss. Colonoscopy reveals
transmural inflammation and skip lesions.
A. Ulcerative colitis
B. Crohn disease
, C. Irritable bowel syndrome
D. Diverticulitis
Answer: B. Crohn disease
Explanation: Skip lesions and transmural inflammation are characteristic of Crohn disease.
Question 11
A 68-year-old woman presents with sudden vision loss and a curtain-like shadow across her visual
field.
A. Cataract
B. Retinal detachment
C. Glaucoma
D. Macular degeneration
Answer: B. Retinal detachment
Explanation: Sudden painless vision loss with a curtain-like visual defect suggests retinal
detachment.
Question 12
A 50-year-old man develops severe chest pain after cocaine use. ECG shows ST-segment elevation.
A. Coronary vasospasm causing myocardial infarction
B. Pericarditis
C. Aortic stenosis
D. Pulmonary fibrosis
Answer: A. Coronary vasospasm causing myocardial infarction
Explanation: Cocaine stimulates sympathetic activity causing coronary vasoconstriction and
increased myocardial oxygen demand.
Question 13
A 7-year-old boy has recurrent infections with encapsulated organisms. Laboratory studies show
absent B cells.
A. T-cell deficiency
B. B-cell deficiency
C. Complement deficiency
D. Neutrophil dysfunction
Answer: B. B-cell deficiency
Explanation: B-cell deficiencies impair antibody production and increase susceptibility to
encapsulated bacterial infections.
