Situs inversus totalis is an inherited condition characterized by a mirror-image transposition of thoracic and abdominal organs. It often coexists with other anatomical variations. Transposition of the organs imposes special demands on the diagnostic and surgical skills of the surgeon. We report a case of a 34-year-old female patient presented with left upper quadrant pain, signs of acute abdomen, and unknown situs inversus totalis. Severe acute cholecystitis was diagnosed, and an uneventful laparoscopic cholecystectomy was performed. A posterior cystic artery was identified and ligated. Laparoscopic cholecystectomy is feasible in patients with severe acute calculus cholecystitis and situs inversus totalis; however, the surgeon should be alert of possible anatomic variations.