The epithelial cell adhesion molecule (EpCAM) is a pan-epithelial differentiation antigen that is expressedon almost all carcinomas. However, a role in rat liver carcinogenesis has never been reported previously.Thus, its expression was investigated herein in rat liver tumors induced by diethylnitrosamine (DEN).Twenty male 5-week-old F344 rats were used in this experiment. Mini-osmotic pumps containing dosesof 47.5 mg of DEN were inserted into the abdominal cavity of each animal to initiate liver carcinogenesis.All animals were sacrificed at 26 weeks after DEN treatment. At necropsy, hepatic masses were processedfor histopathological examination, which revealed forty-four hepatocellular adenomas (HCAs) and twentyhepatocellular carcinomas (HCC). Tumors were immunohistochemically analyzed for EpCAM, proliferatingcell nuclear antigen (PCNA) and co-localization of the two. EpCAM expression was mainly detected inhepatic tumor cells, showing a cytoplasmic staining pattern. However, expression was also slightly observedin normally-appearing surrounding hepatic cells. PCNA expression was highly detected in tumor cells,showing nuclear staining. Double staining of EpCAM and PCNA in tumors showed many cells with colocalization.Taken together, EpCAM and PCNA expression were increased in DEN-induced tumors andmany tumor cells showed co-expression. It is suggested that EpCAM may increase during DEN-inducedtumors, possibly associated with cell proliferation.