The human c-erb B2 proto-oncogene (Her2/ ) encodes a 185-kD transmembrane putative growth factor receptor of the tyrosine kinase family. Overexpression or amplification of this oncoprotein/oncogene has been established in breast, ovarian, salivary gland, and gastric carcinomas and has been implicated in other neoplasms. Recently, overexpression of c-erb B2 has been demonstrated in hepatocellular carcinoma using enzyme-linked immunosorbent assay. Patients with hepatocellular carcinoma have a poor prognosis, and overexpression of c-erb B2 may have prognostic and treatment implications. The authors evaluated the expression and amplification of c-erb B2 in hepatic neoplasms utilizing routine immunohistochemistry and fluorescence in situ hybridization. Formalin-fixed paraffin-embedded tissue sections from 27 hepatocellular carcinomas and 7 hepatocellular adenomas were immunostained with anti-c-erb B2 utilizing a modified avidin-biotin technique following heat induced antigen retrieval. Ten sections from hepatocellular carcinomas were subjected to fluorescence in situ hybridization assay. Positive and negative controls stained appropriately. Slides were evaluated independently by two pathologists. None of the hepatocellular carcinomas or hepatocellular adenomas was immunoreactive with anti-c-erb B2. Adjacent cirrhotic liver parenchyma, present in 11 cases, was also uniformly negative. None of hepatocellular carcinomas showed any evidence of c-erb B2 amplification by fluorescence in situ hybridization. Immunoreactivity for c-erb B2 was not demonstrated in hepatocellular adenomas, cirrhotic livers, or hepatocellular carcinomas using routine immunohistochemical methods. C-erb B2 amplification was not demonstrated in hepatocellular carcinomas. Neither overexpression nor amplification of c-erb B2 (Her2/ ) can be regarded as a useful prognostic factor in hepatocellular carcinoma.