Hepatocellular carcinoma (HCC) is the most common primary liver cancer and its diagnosis on routine stains is usually straightforward, except in some cases where there may be difficulty in distinguishing HCCs from metastatic carcinomas (MC) and cholangiocarcinomas (CC). Hepatocyte Paraffin 1 antibody (Hep Par 1) is a new monoclonal antibody which reacts with normal and neoplastic hepatocytes, and this study aims to determine its specificity and sensitivity in distinguishing hepatocellular carcinoma (HCC) from cholangiocarcinoma (CC) and metastatic carcinomas (MC). Hep Par 1 antibody was applied to 28 cases of HCC, 22 cases of MC from varying sites and 8 CCs, and produced a strong, diffuse, granular, cytoplasmic staining of all benign hepatocytes. 23 out of 28 cases of HCC showed heterogeneously positive staining for Hep Par 1 irrespective of their degree of differentiation, while 2 out of 8 cases of cholangiocarcinoma were positive for Hep Par 1, and all 22 cases of metastatic carcinoma were negative. The sensitivity and specificity of Hep Par 1 for HCC was 82.1% and 93.3% respectively; whereby the antibody was noted to show occasional false positivity in cases of cholangiocarcinoma and non-neoplastic bowel mucosa, while its variable staining in HCC produced false negative results in some small biopsies. Thus, Hep Par 1 should be used in a panel with other antibodies to obtain useful information in distinguishing HCC from CC and MC.