A 63-year old man was referred to our hospital because of fever, appetite loss, and increased biliary enzyme levels. Upper gastrointestinal endoscopy revealed a tumor in the duodenal papilla, diagnosed as an adenocarcinoma via biopsy, and computed tomography (CT) revealed multiple tumors in the liver. Chemotherapy with TS-1 was initiated based on a diagnosis of ampullary cancer with multiple liver metastases. After TS-1 treatment, the multiple tumors were no longer detectable, and the primary tumor did not increase in size for 4 years. At this time, however, the patient experienced fever, jaundice, and appetite loss. The hepatic mass was not detected via CT or MRI. The primary tumor was determined to be resectable; therefore, we performed subtotal stomach preserving pancreatoduodenectomy. The patient was discharged 55 days after surgery and is alive without recurrence 2 years after surgery.