In order to clarify the pathological significance of Mallory body (MB) formation in human hepatocellular carcinoma (HCC), cell nuclear deoxyribonucleic acid (DNA) content was measured microspectrophotometrically in 20 autopsied cases of HCC associated with cirrhosis and bearing many MBs. According to the degree of dispersion, the DNA histogram was classified into type I (diploid pattern), type II (hyperploid pattern) and type III (aneuploid pattern). Non-neoplastic hepatocytes of normal livers and of cirrhotic areas of the 20 HCC cases showed generally a diploid pattern (type I). In contrast, MB-positive HCC cells showed more hyperploidy or aneuploidy (type I: 0%; type II: 35%; and type III: 65%) compared with MB-negative HCC cells (type I: 25%; type II: 50%; and type III: 25%). These data suggest that MB formation in HCC is accompanied by a constant change of DNA content of HCC cells, though the causal relation between them is only speculative. Two separate HCC nodules in the same liver, both of which contained many MB-positive cells, showed the same type of DNA histogram pattern, suggesting the possibility that they were of a monoclonal origin and had spread discontinuously in the liver.