To study the Hoxa-13 gene in the liver, we examined its expression by RT-PCR in various liver cell lines, rat livers under different conditions, and human primary hepatocellular carcinomas (HCCs), The gene was found to be expressed in cell lines originating from liver stem-like cells, but not in cell lines originating from hepatocytes and bile duct epithelia, Expression was induced in rat livers after treatment with D-galactosamine, which is known to induce oval cell proliferation, but not after a two-thirds partial hepatectomy (2/3 PH) where induction of oval cell proliferation is thought not to occur. Expression of the gene correlated with human HCC samples associated with Hepatitis B or C virus infection in this small series. These results suggest that the Hoxa-13 gene may provide a potentially useful tool for elucidation of mechanisms involved in lineage-specific differentiation and carcinogenesis of liver stem cells.