Histopathological differentiation between hepatocellular adenoma and well differentiated hepatocellular carcinoma (HCC) may be a difficult task in small biopsies and occasionally in resected tumor specimens. Whether the analysis of chromosome aberrations can contribute to a more precise discrimination has not been analyzed systematically up to now. Therefore, fluorescence in situ hybridization was applied to 28 cases of adenoma and well differentiated carcinoma, using centromeric probes for chromosomes 1, 6, 7, 8, and X. None of 14 adenomas revealed an aberrant count in the analyses performed. By contrast, 13/14 carcinomas demonstrated aberrations for 2-5 chromosomes/case. Chromosome 1 was aberrant in 8/12 cases informative for this probe (67%), chromosomes 6 and 7 were aberrant in 9/14 cases (64%), chromosome 8 was aberrant in 11/14 cases (79%), and chromosome X in 7/14 cases (50%). Taking results for chromosomes 1 and 8 together, 13/14 HCC revealed aberrations for at least one of these chromosomes. Probes for 6, 7, and X revealed no additional aberrant cases.Thus, FISH for chromosomes 1 and 8, extended by probes for chromosomes 6, 7 and X, represents a promising approach toward a more accurate differentiation between hepatocellular adenoma and carcinoma.