Background: Ampullary adenoma is glandular dysplastic lesions that arise in and around the duodenal ampulla. Endoscopic ampullectomy is the treatment of choice for an ampullary adenoma. However, regenerative tissue developed at the post-ampullectomy site can mimic the ampullary adenoma. Methods: We retrospectively reviewed the medical records of a patient treated for the ampullary adenoma. Results: A 67-year-old woman underwent screening esophagogastroduodenoscopy. A protruding mass-like lesion was found at the ampulla of Vater (Figure A). Histological examination of the lesion revealed tubular adenoma with low grade atypism (Figure B). An endoscopic snare ampullectomy was performed. The microscopic ampullectomy specimen showed the adenoma, and the margin of specimen was free of the adenoma. Forty days after the ampullectomy, the patient visited the emergency department due to fever and abdominal pain. Acute cholangitis was suspected from the clinical fi ndings. Endoscopic retrograde cholangiopancreatography was performed, and a recurrent protruding mass was found at the ampulla (Figure C). We performed an ampullectomy again suspecting that this lesion was recurrent or remnant adenoma. However, the ampullectomy specimen revealed the regenerative epithelium, not true adenoma (Figure D). Conclusions: In cases of such as this, where an ampullectomy has been performed recently and the margin is absent in histology, we have to consider the possibility of the mass to be regenerative tissue.