Fluorescence in situ hybridization performed on tissue sections can reveal chromosomal abnormalities related to histopathological features. This technique was performed on serial frozen sections from seven normal livers and 29 hepatocellular carcinomas (HCCs) using pericentromeric repeat-specific probes for chromosomes 1, 4, 6, 7, 8, 16, and 17. For each HCC and each probe, the percentage of cells showing one, two, or more than two signals was counted and compared with the distribution in the normal liver. According to these results, HCCs were categorized as monosomic, disomic, or polysomic (more than two signals) for the chromosome tested. These data were compared with the main histopathological characteristics of HCC. Chromosome gains were very common, preferentially affecting chromosome 1 (23 of 27 cases, 85%), chromosome 16 (16 of 27 cases, 59%), chromosome 7 (16 of 29 cases, 55%), chromosome 6 (15 of 29 cases, 52%) and chromosome 8 (14 of 29 cases, 48%). Monosomy was seen more rarely, affecting preferentially chromosome 16 (19%), chromosome 17 (14%), and chromosome 4 (10%). A significant correlation was observed between aneusomy of chromosome 4 and tumor size (P < .05) or the presence of vascular embolism (P < .05). In conclusion, chromosomal gains are frequent genetic events in human HCC. A significant association between a gain in chromosome 4 and large tumor size or vascular embolism suggests that this genetic abnormality is a late event in liver carcinogenesis.