An 81-year-old Japanese woman with a medical history of type II diabetes mellitus and arteriosclerosis obliterans was referred to our hospital for investigation of the frequent elevation of hepatic and biliary enzymes and dilatation of the intrahepatic bile ducts, which were identified by her family doctor during abdominal ultrasonography. The patient did not complain of abdominal pain or decreased appetite. Laboratory examinations revealed slightly elevated biliary enzymes, including 413 IU/L alkaline phosphatase (normal, 104–338 IU/L) and 184 IU/L -glutamyl transpeptidase (normal, 9–28 IU/L); however, other serum chemistry data were within normal limits. Levels of the serum tumor markers carcinoembryonic antigen and carbohydrate antigen 19-9 were also within normal limits. Contrast-enhanced abdominal computed tomography and magnetic resonance cholangiopancreatography showed dilatation of the intra- and extrahepatic bile ducts and the main pancreatic duct without any strictures, suggesting the presence of an ampullary tumor. Neither lymph node enlargement nor metastasis was observed. Endoscopic ultrasonography showed a hypoechoic mass of 9 × 9 mm in the ampulla of Vater. The tumor was located on the inside of the duodenal wall and had not invaded the duodenal muscularis propria, pancreas, common bile duct terminal, or main pancreatic duct. Duodenoscopy revealed a bulging oral protrusion because of the dilated distal bile duct and an exposed reddish tumor at the ampulla of Vater, which was diagnosed on biopsy to be adenocarcinoma with the SCC component. Endoscopic retrograde cholangiopancreatography (ERCP) showed dilatation of the upstream bile duct and main pancreatic duct, and ERCP followed by transpapillary biliary intraductal ultrasonography revealed a hypoechoic tumor confined within the ampullary portion of the duodenum, the common channel of the ampulla, and the ampullary portion of the bile duct area. However, no extension into the ampullary portion of the pancreatic duct or the distal bile duct was observed. Because the patient showed the onset of acute cholangitis secondary to ERCP, endoscopic retrograde biliary drainage was performed using a plastic stent on the day after ERCP. Based on these findings, the lesion was diagnosed as early-stage carcinoma of the ampulla of Vater with the SCC component without extension along the distal bile duct or main pancreatic duct. Subsequently, pylorus-preserving pancreaticoduodenectomy (PPPD) with regional lymph node dissection was performed. Macroscopic examinations revealed a whitish and solid exposed-type tumor, 11 × 8 mm in size in the ampulla of Vater. Pathological examinations showed the presence of two malignant components, including poorly differentiated tubular adenocarcinoma and SCC without invasion beyond the sphincter of Oddi or into the duodenal submucosa. SCC and adenocarcinoma components in the tumor comprised approximately 30 and 70 % of the tumor mass, respectively. No regional lymph node metastases or lymphovascular or perineural infiltrations were observed. Immunohistochemistry (IHC) analyses of the squamous marker cytokeratin (CK)-5/6 showed strong positive expression in the SCC component and slight expression in the adenocarcinoma component. In contrast, the adenocarcinoma marker CK-7 was strongly detected in the adenocarcinoma component and weakly detected in the SCC component. The postoperative course was uneventful and the patient experienced no tumor recurrence or metastasis until 20 months following surgery.