Rationale:Adenomyoma is a rare reactive, hamartomatous benign tumor-like lesion. Although adenomyoma can occur anywhere in the gastrointestinal tract, including the gallbladder, stomach, duodenum, and jejunum, it is very rarely observed in the extrahepatic bile duct and ampulla of Vater (AOV). The preoperative accurate diagnosis of adenomyoma of the Vaterian system, including the AOV and common bile duct, is significant to appropriate patient management. However, discriminating between benign and malignancy is highly challenging. Patients are frequently mistaken as having periampullary malignancy, thereby leading to unnecessary extensive surgical resection with a high risk of complications.Patient concerns:A 47-year-old woman visited a local hospital owing to epigastric and right upper-quadrant abdominal pain for 2 days.Diagnoses:Abdominal ultrasonography performed in the local hospital revealed suspicious of a distal common bile duct malignancy. She was transferred to our hospital for further evaluation and management.Interventions:After consulting with the patient, a multidisciplinary team, including a gastroenterologist, finally decided to perform surgery under the impression of an ampullary malignancy, and pylorus-preserving pancreatoduodenectomy was performed without any complications. She was histopathologically diagnosed with an adenomyoma of the AOV.Outcomes:At the 5-year follow-up, she was well and did not develop further symptoms or complications.Lessons:Although adenomyoma is very rare, it should be included in the differential diagnosis of mass-like lesions of the AOV to avoid unnecessary surgeries.