A 62-year-old woman was treated with sunitinib as a second-line therapy for metastatic clear-cell renal carcinoma. She was given oral sunitinib 50 mg once daily, 4 weeks on followed by 2 week off. During the fourth week of her first cycle, the patient was admitted to our hospital because of an acute-onset, right upper quadrant pain associated with nausea and vomiting. She was diagnosed with acute acalculous cholecystitis, which was treated with broad-spectrum antibiotics, and sunitinib therapy was discontinued. A follow-up computed tomography scan of the abdomen revealed a complete resolution of gallbladder changes. Our patient did not have major risk factors for developing an acalculous cholecystitis except for a relative immunosuppressed state secondary to her advanced renal cancer. The Naranjo Adverse Drug Reaction Probability Scale score for this event was 5, indicating a probable association of the event with sunitinib. Because the use of sunitinib is expanding in clinical practice, we want to alert the oncology community about this uncommon and life-threatening complication in patients receiving sunitinib or another agent with antiangiogenic activity.