Villous adenomas of the duodenum are rare, and malignancy is discovered in about 30% of the lesions. The authors describe two cases of villous adenoma of the second portion of the duodenum (13 and 8 cm in diameter). The diagnosis was obtained through endoscopy, which did not demonstrate any malignant change. In both patients, malignant change was shown by intraoperative frozen sections, and a pancreatico-duodenectomy was performed. Review of the literature and the authors' experience indicate endoscopic biopsies do not rule out the presence of malignancy in adenomatous pathology of the duodenum. Therefore, laparotomy should be performed whenever endoscopic excision of the neoplasm is not feasible. The authors emphasize the importance of an intraoperative diagnosis based on accurate frozen sections and propose a correct procedure to obtain the best results.