In an attempt to provide a quantitative basis for differentiation between well-differentiated hepatocellular carcinoma and hepatocellular carcinomalike lesions (focal nodular hyperplasia, regenerative nodular hyperplasia and hepatocellular adenoma), histopathological and morphometrical analyses were performed on 208 cases of various liver diseases with the aid of an image analyzer. As practical indicators for hepatocellular carcinoma, the following six morphometrical features were established: (a) nuclear shape factor of less than 0.93, (b) coefficient of variance of nuclei of more than 5%, (c) average width of trabecular cords greater than three cells, (d) nucleocytoplasmic ratio increased to more than 0.3, (e) cellular density of more than 40 liver cells and (f) individual nuclear dimension larger than 50 microns2. The manifest categories increased with dedifferentiation of cells in hepatocellular carcinoma; the number and degree of cellular and structural atypia became more prominent. Data were analyzed statistically by two multivariate analyses. Logistic analysis was able to correctly separate hepatocellular carcinoma from conditions that were not hepatocellular carcinoma, including hepatocellular carcinomalike lesions. The incidence of 13 descriptive histopathological findings such as fibrous capsule, portal triads and clear-cell clusters were also compared in hepatocellular carcinomalike lesions and hepatocellular carcinomas graded according to Edmondson's classification. Presence of a fibrous capsule, portal triads, mosaiclike patterns and tumor vessels showed statistical differences between hepatocellular carcinomalike lesions and well-differentiated hepatocellular carcinoma by the chi 2 test (p less than 0.005).