To demonstrate DNA clonal heterogeneity of hepatocellular carcinomas (HCC), the DNA histographic pattern of both primary HCCs and their recurrent or metastatic lesions were studied among 36 patients (33 men and 3 women). Thirty-six paired aspirations or imprints taken from primary, recurrent or metastatic lesions were stained, using the modified Feulgen method, and the DNA content was measured with a scanning microdensitometer at a wavelength of 550 nm. Paired aspirations or imprints taken from different parts of the same HCC were examined in 17 cases; the DNA distribution patterns were similar in 15 (88%) and differed in only two (12%). A similar DNA histogram was also shown among different tumors in 10 (71%) of 14 patients with multiple HCCs, with a DNA ploidy discrepancy in only four (29%). Two of two subcutaneous metastases and two of three recurrent tumors showed DNA distribution patterns similar to those in their primary HCCs. In summary, a DNA clonal heterogeneity of HCC was found in 19% (7/36). In contrast, the similar DNA histographic patterns found in most instances among different parts of the HCC and between the primary and recurrent or metastatic lesions suggest that HCC may derive from a single cell clone in the majority of cases.