Eighteen patients with a biliopancreatic carcinoma in 15 different cancer family syndrome (CFS) families were studied. Only families with three or more first-degree relatives with colorectal carcinoma were included, and other characteristics of CFS were required in at least two cases. In 14 patients, the histologic specimen was available for reevaluation. In 11 (79%), the tumor was confirmed as a carcinoma of the biliary tract or papilla of Vater. In three (21%), carcinoma of the pancreas was the most probably alternative. In all four patients without histologic reevaluation, the diagnosis had been carcinoma of the biliary tract. This study suggests that carcinoma of the biliary tract or papilla of Vater is associated more commonly with CFS than with carcinoma of the pancreas. In this respect, CFS resembles familial adenomatosis coli, in which this association previously has been established.