A case of multiple villous and, more rarely, tubulovillous adenomas of the main pancreatic duct, associated with a diffuse infiltrating adenocarcinoma of the pancreas in which evidence for a link between these lesions is supported by histopathologic features, is reported in a 53 year old patient. Clinical presentation included abdominal pain, weight loss and chronic diarrhea with steatorrhea related to pancreatic insufficiency. Retrograde endoscopic pancreatography showed a complete stenosis of the main pancreatic duct located 3 mm beyond the ampulla of Vater. CT scan showed an heterogeneous cephalic pancreatic tumor with extensive enlargement of the main pancreatic duct. After total pancreatectomy, recovery was maintained (follow-up 18 months). By analogy to colorectal tumors, a new pathologic classification of these rare neoplasms may be proposed.