Hepatocellular carcinomas (HCC) of various differentiation, Edmondson (Edm) grade I-IV, often based upon viral infectious hepatitis transformed through regeneration, nodular and/or dysplastic adenomatous hyperplasia. Aspiration cytology, even needle biopsy for such lesions, is very difficult to interpret. We have been studying multiparametric cytologic analysis using DAPI/Hematoporphyrin (HP) staining for the cece samples provided from exactly trimmed 50-microns thick paraffin sections, employing a new software program which we developed, combining DNA ploidy and cell protein content analysis with morphometry. DAPI indicates DNA content and nuclear size and HP indicates cell protein content and cell size. From 21 cases of HCC, 43 nodules or masses including multiple lesions and nodule in nodule were analyzed. Surrounding non-neoplastic hepatic tissues were examined as the control specimens. On DNA histogram, cases with the peak over 2.4 c are identified as aneuploid (Aneupl). Cases of Edm I, or II, 6 of 8 samples showed Aneupl., all of 11 cases of Edm II, 11 cases of Edm III, and one of Edm IV showed Aneupl. Multinodular foci in the same cases and also nodule in nodule often showed different modes of Aneupl. This suggested heterogenetic carcinogeneity. Noncarcinomatous foci often showed Aneupl. modes, which may indicate malignant transformation or malignant potential.