Optimum cutoff levels for plasma des-γ-carboxy (abnormal) prothrombin (DCP) and serum α-fetoprotein (AFP) were determined by analyzing receiver operating characteristic (ROC) curves to discriminate between hepatocellular carcinoma (HCC) and benign hepatic conditions. Plasma DCP levels in 200 patients with HCC and 197 control patients with benign liver diseases were measured by an enzyme immunoassay with anti-DCP monoclonal antibodies, while serum AFP levels for both groups were measured by radioimmunoassay. From ROC curves and tangential lines with a slope of 1.0, the cutoff levels of DCP and AFP were determined to be 0.11 AU/ml and 150 ng/ml, respectively. Lowered cutoff levels of DCP did not improve the sensitivity, in contrast to the increased sensitivity obtained by lowering the specificity of AFP. The sensitivities and specificities determined in this study were close to the currently used values of 0.1 AU/ml for DCP and 200 ng/ml for AFP, justifying these cutoff levels for the differentiation of benign and malignant liver diseases.