We have previously demonstrated increased levels of insulin-like growth factor (IGF)-II mRNAs and protein with re-expression of a fetal pattern of transcripts in human hepatocarcinoma. In the present study, we have investigated IGF-II transcripts and protein in liver tissues from patients with hepatocarcinoma infected with hepatitis B virus, by using in situ hybridization and immunohistochemical techniques. The IGF-II transcripts and protein have been localized to the hepatocytes, be they normal or tumoral with a gradient for IGF-II expression from normal to dysplastic and tumoral tissues. Hepatitis B virus mRNAs and viral surface antigen have only been detected in some hepatocytes in the peritumoral tissues. Therefore, the results show expression of IGF-II in hepatocytes. The increase of IGF-II expression in tumor hepatocytes support the hypothesis that it might represent a marker of hepatocytes differentiation.