Extrahepatic neoplasms metastatic to the liver histologically are often indistinguishable from hepatocellular carcinoma (HCC). The differential diagnosis between HCC and metastatic liver tumours can be even more difficult in ultrasound guided fine-needle biopsies. Purpose of the present study was to investigate the utility of immunohistochemical staining with polyclonal anticarcinoembryonic antigen (pCEA) antibody and of in situ hybridization (ISH) revealing human albumin mRNA, with emphasis on tissues obtained via fine-needle procedure. Cases consisted of 52 primary HCC; 2 HCC metastatic to vertebral bones; 18 tumours metastatic to the liver; 24 non-hepatocellular tumours metastatic to the skin, lymph nodes and brain; 2 immature teratomas with areas of hepatoid differentiation. Forty-seven HCC (90%) and 7 liver metastases (38%) were obtained by ultrasound guided fine-needle biopsies (21 g needle was used). All the remaining cases were surgical specimens. All the cases were studied with immunohistochemistry for pCEA and ISH using a cRNA probe for human albumin mRNA. The immunohistochemical staining using pCEA showed a canalicular type of positivity in 37 cases of HCC (71%), in one HCC metastatic to vertebral bone and in the hepatoid areas of one immature teratoma. No canalicular type of positivity was obtained in non-hepatocellular neoplasms metastatic to the skin, brain, lymph-nodes and liver. Albumin mRNA was detected in 51 (98%) primary HCC, in both HCC bone metastases, and in the hepatoid areas of both immature teratomas. No positivity was obtained in non-hepatocellular tumours. The data here obtained indicate that immunostaining with pCEA and ISH revealing human albumin mRNA are markers of hepatocellular differentiation and confirm their diagnostic utility. Detection of albumin mRNA showed a higher sensitivity. In addition the cRNA probe here used seems more sensitive that the oligonucleotide probes employed in previous studies.