Nineteen cases of villous tumors of the duodenum are reported. They have a predilection for the ampullary region, tend to present with obstructive jaundice, especially if malignancy is present, and have a high prevalence of cancer (12 of 19, or 63%). Even when biopsies are available, the diagnosis of cancer is frequently missed (5 of 9 proven cancers, 56% false-negative rate), and it may be impossible to assess the presence of carcinoma in situ or invasive carcinoma without complete excision of the lesion. The authors' experience suggests that some small benign ampullary villous adenomas or those with carcinoma in situ can be excised locally but that pancreaticoduodenectomy is preferable in the fit patient for better local control both of extensive benign lesions and cancers without distant metastases.