Acute cholecystitis severity ranges from mild to very severe, and its most dreadful complication is gallbladder empyema. It can be caused by several etiologic agents, but Mycobacterium tuberculosis is not common among them. Here we present a 61-year-old female who lives in an area of high tuberculosis endemicity and has type 2 diabetes mellitus. She came to our hospital with a 2-day history of moderate-to-severe colicky right upper quadrant abdominal pain and other clinical manifestations compatible with AC. Imaging studies confirmed the diagnosis. An emergency open cholecystectomy was performed and the gallbladder was sent for histopathologic examination. M. tuberculosis was identified by molecular studies and the treatment was adjusted. The patient recovered uneventfully. The clinical history and physical examination are essential for raising the index of suspicion, but complementary evaluation with imaging studies is necessary to confirm the diagnosis and evaluate its complications. Tuberculosis is a major health problem worldwide, and health professionals should be aware of its clinical spectrum to approach and manage common and uncommon presentations within their scope of attention.