Twelve cases of fibrolamellar hepatocellular carcinoma (FLC) were evaluated for DNA ploidy by means of image analysis of Feulgen-stained tissue sections. All of the tumors showed a nondiploid DNA distribution (six aneuploid and six tetraploid); no diploid pattern was found. The nuclear area of the tumors (53.8 microns 2 +/- 18.0; mean +/- standard deviation) was significantly larger than that of the surrounding noncancerous livers (33.2 +/- 4.7; P < .0001). These findings suggest that DNA content in fibrolamellar carcinoma (FLC) is not directly related to the clinical behavior and that other factors may be responsible for the better prognosis of this variant of HCC.