A 71-year-old man complained of loss of appetite 6 months before his visit to our hospital, had lost 9 kg of weight in 2 months, and had white stools, so he was brought to a referring physician. The patient was referred to our hospital for careful examination and treatment. He had no past history or family history of malignancy. He had a drinking habit and a smoking habit of approximately 15 cigarettes per day. At the initial visit, he complained of loss of appetite and physical weariness. Blood tests were normal, including carcinoembryonic antigen (CEA) of 2.4, IgG4 of 51.1. The carbohydrate antigen 19-9 (CA 19–9) mildly elevated of 49.7. Enhanced computed tomography (CT) revealed the stenosis in the third portion of the duodenum, main pancreatic duct dilatation, and atrophy of the pancreatic head. Upper Gastrointestinal (GI) endoscopy was also performed, which revealed one-third circumferential mucosal irregularity from the anal side of the main duodenal papilla to the inferior duodenal angulus, which bled easily. A biopsy was performed from the same site. Severe stenosis was observed from the inferior duodenal angulus to the third portion, and the scope could not pass through it. The contrast medium also could not pass through the stenosis and refluxed into the stomach. The biopsy revealed inflamed duodenal mucosa, and no malignant cells were found. As described above, the initial findings of examinations were suspicious for duodenal stenosis caused by duodenal tumor or pancreatic head tumor. Moreover, endoscopic ultrasonography (EUS) was performed for close examination. The main pancreatic duct was stenosed at the pancreatic head, which measured approximately 10 mm in diameter at the transition area of the pancreatic head body. A hypoechoic area at the deep lesion of pancreatic head, approximately 20 mm was suspected at the narrowing of the main pancreatic duct, but tumor evaluation was difficult. We considered performing endoscopic ultrasound-guided fine needle aspiration (EUS–FNA) on the same area; however, the presence of the artifact made it difficult to perform a detailed evaluation. Furthermore, the stenosis at the third portion of the duodenum made it difficult to secure a safe surgical field for puncture. Therefore, EUS–FNA was not feasible owing to technical reasons. Although preoperative histological diagnosis was impossible, we diagnosed pancreatic head cancer or duodenal cancer based on imaging findings. Regarding the treatment plan, as the patient was predicted to have advanced cancer based on the results of preoperative enhanced CT and GI endoscopy and the patient continued to have difficulty with oral intake due to duodenal stenosis, we decided to perform pylorus-preserving pancreatoduodenectomy (PPPD) as a diagnostic treatment. Intraoperative findings: Upon opening the abdomen, abdominal cavity had no obvious nodules or ascites. Liver metastases and peritoneal dissemination were absent, as confirmed by detailed intraperitoneal observation. Initially, rapid peritoneal lavage cytology was performed, and the results were negative. A firm mass was palpable on the third duodenal portion, and a white nodule was observed on the serosal surface in a partially distal direction. Visual examination showed that duodenal cancer was the more likely diagnosis. Moreover, no unresectable component was noted at that point. PPPD was conducted as scheduled without performing intraoperative rapid pathology diagnosis. The mesentery of the transverse colon was partially resected. No obvious lymph node enlargement was noted. PPPD, D2 Lymph node dissection, and modified Child procedure (operation time, 5 h 44 min; amount of bleeding, 610 ml) was performed without problem. The resected specimen showed a 40 × 30 mm tumor on the descending part of the duodenum slightly more distal to the papilla of Vater, and a white thickening of the duodenal wall was observed on the sectioned surface of the same area. Histopathological findings: Primary duodenal carcinoma, pT4, pN2(#12b,#17a,#17b), cM0, pStage IIIB (Union for International Cancer Control 8th edition), intraductal papillary mucinous neoplasm (IPMN). A 14-mm flat prominence was protruding into the lumen on the distal side of the papilla of Vater and tubular development similar to the gastroduodenal gland. On the same area, there was an infiltrative growth of carcinoma cells with a predominant component of well to poorly differentiated tubular adenocarcinoma under the normal duodenal mucosa. The non-tumor duodenal epithelium is observed in the upper right corner of the image, showing the continuous infiltration of the intramucosal hypodense lesion into the submucosal layer of the duodenal epithelium. In addition, immunostaining of the same area showed that MUC5AC, which stained the gastric crypt epithelium, was diffusely positive in the intramucosal and tumor-infiltrated area, whereas MUC6 was negative to partially positive in the mucosa and positive in approximately 50% of the infiltrated area.. MUC2 was negative in all cases. These pathological findings indicated the presence of a transition zone between ectopic gastric mucosa and normal mucosa in the duodenal lesion. No malignancy was found in the pancreas, and cancerous infiltration was observed around the papilla of Vater, but not around the stenotic area of the main pancreatic duct. On the contrary, an IPMN was noted in the branch pancreatic duct, which was covered with low-grade to high-grade columnar epithelium. Based on the EUS findings, the hypoechoic region was drawn at the deep lesion of the pancreatic head. Moreover, EUS may have drawn the duodenal carcinoma in the third portion beyond the pancreatic head, as noted from a retrospective view. No cancer cells were detected in the stenosis area of the main pancreatic duct during pathological examination. Pathologically, the cause of the main pancreatic duct stenosis was not duodenal carcinoma or pancreatic head carcinoma. The apparent cause remains unclear. Intraoperative findings showed that the pancreas itself was hard, and the cause may have been spillover of inflammation caused by duodenal stenosis. Therefore, this case was considered primary duodenal carcinoma arising from ectopic gastric mucosa. Postoperative course: The patient resumed oral intake on postoperative day 5, and the intraperitoneal drains were removed sequentially on postoperative day 8. He was discharged home on postoperative day 29 without any problem. On postoperative day 38, the drug combination TS-1 (tegafur/gimeracil/oteracil potassium), an oral 5-FU drug, was started as adjuvant chemotherapy. The patient continues to receive treatment without adverse events, and the CA19-9 values were 13.5 and a10.0 at 2 and 6 months postoperatively, respectively. He is alive and recurrence-free 7 months after surgery.