Distribution of Lewis(x) (Le(x)) and Lewis(y) (Le(y)) blood-group antigens was studied in nine formaldehyde-fixed, paraffin-embedded cholangiocarcinomas (CCs), 26 hepatocellular carcinomas (HCCs), and eight normal livers. All CCs, with one exception, expressed both Le(x) and Le(y) antigens on few or many cells. In HCCs Lex was expressed infrequently (8%), while Le(y) was detected in 31% of cases. Both markers, when present in HCCs, tended to be spotty. Fibrolamellar carcinomas and normal livers did not react with either Le(x) or Le(y) antigens; however, Le(y) antigen was observed occasionally in bile duct epithelial and ductular cells. In conclusion, inappropriate tissue distribution of Le(y) blood-group antigens was observed in CCs and, much less frequently, in HCCs. The high frequency of Le(x) antigen in CCs but not in HCCs may help in the differential diagnosis of these two tumors.