Invasive upper gastrointestinal adenocarcinoma was found in 57 (4.5%) of 1255 patients with familial adenomatous polyposis, recorded in 10 registries. The most frequent sites were duodenum in 29, pancreatic ampulla in 10, and stomach in 7. These findings confirm an increased risk of upper gastrointestinal cancer in the polyposis patient, particularly distal to the pylorus, and support an adenoma-carcinoma sequence. Regular surveillance of the upper gastrointestinal tract is essential in patients with familial adenomatous polyposis.