This report deals with two cases of villous adenoma of the Wirsung duct. The two patients presented with upper abdominal pain, diarrhea, and weight loss. Duodenal intubation showed a complete failure of exocrine pancreatic function. Ultrasound scan, computed tomography, and endoscopic retrograde cholangiopancreatography disclosed marked dilatation of the head portion of the main pancreatic duct. A proximal duodenopancreatectomy was performed. Pathological examination revealed a papillary polyp expanding the pancreatic head and filling the main duct lumen. Histological pattern consisted of a villous adenoma without any feature of malignant change. Previously reported cases exhibit many similarities to our two cases. The putative likelihood of malignant change and the relationship between villous tumors of the Wirsung duct and of other origin remain unclear.