In a retrospective study (1982-1990), 12 adenomas, 35 carcinomas of the papilla of Vater, and 21 duodenal adenomas were examined. All patients had endoscopicbioptic examinations (5-10 forceps biopsies, snare biopsy or forceps-biopsies after endoscopic sphincterotomy). Special attention was paid to malignant transformation of adenomas and of residual adenomatous tissue in surgical resected cancer. Follow-up data were gained by reexamination or questionnaires. In papillary adenomas, an adenocarcinoma was found in 30% at operation or by follow-up. In 41.2% of the operated cases, residual adenomatous tissue was found, more often in well-differentiated adenocarcinomas than in other histological types. A transformation from duodenal adenomas to adenocarcinomas was seen less frequently (9.5%). Therefore, the risk of malignancy in ampullary adenomas is greater than elsewhere in the duodenum. In eight of 11 patients (72.7%) with duodenal adenomas, one or more simultaneously developed colonic adenomas were found (in four cases a Gardner syndrome not known before). We conclude that there is strong evidence that most ampullary and duodenal carcinomas develop in preexisting adenomas, with an adenoma-cancer sequence similar to that accepted for colorectal carcinoma. This has to be kept in mind for diagnostic as well as therapeutic reasons. When either an adenoma of the ampulla or duodenum is diagnosed, colonoscopy is mandatory to find or exclude colonic adenomas. In patients with familiar adenomatosis, the duodenum and the papilla of Vater have to be examined endoscopically.