Cadherin-17, also called liver-intestine cadherin, is a calcium-dependent transmembrane glycoprotein that mediates cell-cell adhesion in intestinal epithelium. Expression of cadherin-17 was reported in gastric, pancreatic, and colorectal adenocarcinomas but not in other tumors. Whether cadherin-17 can be used as a marker for diagnosis of cancers is still unclear. In this study, we used immunohistochemical methods to stain cadherin-17 in tissue arrays containing most normal tissues and 518 carcinomas from many anatomic sites. Among normal tissues, the expression of cadherin-17 was limited to epithelial cells of small intestine and colon. Colorectal adenocarcinomas showed staining in 96% of cases and most of them had strong and diffuse staining. Gastric, pancreatic, and biliary adenocarcinomas showed diffuse or scattered staining in about 25-50% of cases. Fewer than 1% of carcinomas outside the digestive system were positive for cadherin-17. When a two-marker, Cadherin-17/cytokeratin 7, profile was used, 37 of 38 (97%) cadherin-17(+)/cytokeratin 7(-) tumors were colorectal adenocarcinomas; 49 of 56 (86%) cadherin-17(+)/cytokeratin 7(+) tumors were gastric, pancreatic, or biliary adenocarcinomas. Our results show that cadherin-17 is a useful immunohistochemical marker for diagnosis of adenocarcinomas of the digestive system.