Heterotopic pancreas, defined as the presence of pancreatic tissue that lacks anatomic and vascular continuity with the pancreas proper, may be more likely to undergo malignant change. However, malignancy arising from heterotopic pancreas is rare. In Korea, only one case of adenocarcinoma arising from a gastric heterotopic pancreas has been reported. Recently, we experienced a case of duodenal carcinoma arising from heterotopic pancreas in a 64-year-old man. Endoscopic biopsy of the stenotic duodenum was positive for adenocarcinoma, and he underwent a pancreaticoduodenectomy with subtotal gastrectomy. Histologic examination of the resected specimen satisfied the proposed conditions that are necessary to prove that a malignancy arose from heterotopic pancreas. Despite an adjuvant chemotherapy, he died 10 months after surgery. Herein, we report a case of duodenal adenocarcinoma arising from heterotopic pancreas with a review of the relevant literature.