A 58-year-old woman complained of painless jaundice. The serology showed total bilirubin 10.6 mg/dL with direct bilirubin of 7.0 mg/dL. Abdominal computed tomography (CT) scan disclosed an abnormal arrangement of the abdominal viscera and dilation of the biliary tree. A nearly 1.4 cm-sized periampullary mass was seen. These findings are compatible with situs ambiguous with polysplenia and were suggestive of a periampullary tumor. Due to her unusual anatomical features, the patient underwent an endoscopic retrograde cholangiopancreatography (ERCP) in the supine position instead of in the conventional prone position. ERCP showed that the common bile duct (CBD) diameter was increased to 20 mm. Microscopic findings of the biopsy specimen of papillary mass were compatible with an adenocarcinoma of the ampulla of Vater. The clinical stage was stage IA (T1N0M0). Eight days later, a papillectomy was carried out by endoscopic snare resection. Six months later, follow-up studies, including ERCP, abdominal CT and 18-fluorodeoxyglucose positron emission tomography ((18) -FDG PET)-CT scan, showed no evidence of recurrence. Although the success rate of supine position ERCP may be influenced by the extent of the intestinal malrotation and the position of the duodenum, we conclude that supine position ERCP can be carried out effectively in a patient with situs anomaly.