A monoclonal antibody highly specific for benign and malignant hepatocytes (HepPar 1) was evaluated as part of an antibody panel used to differentiate hepatocellular from nonhepatocellular neoplasms. Sixty-five liver tumors and two extrahepatic tumors from patients with documented liver tumors were studied. Twenty-two neoplasms were of hepatocellular origin, three were combined hepatocellular/cholangiocarcinomas, and the remainder were of nonhepatocellular origin. HepPar 1 alone had an 82% sensitivity and 90% specificity for the detection of hepatocellular neoplasms. The corresponding values for alpha-fetoprotein were 57% and 97%. Polyclonal antibody to carcinoembryonic antigen (canalicular pattern) had a sensitivity of 79% and specificity of 97% for these tumors. The use of antibody panels provided superior results when compared with individual antibodies. In summary, HepPar 1 monoclonal antibody is a useful reagent for the differential diagnosis of hepatocellular tumors. Its utility is enhanced when it is used as part of a diagnostic antibody panel.