The c-myc and cyclin D1 genes are included among the oncogenes the amplifications of which have been detected in cancers of various organs. However, there have been few reports on the amplification of both these genes in primary and metastatic liver carcinomas. In the present study, c-myc and cyclin D1 gene amplification was examined in 76 primary and metastatic liver carcinomas using formalin-fixed paraffin-embedded tissue sections and a differential polymerase chain reaction procedure. c-myc and cyclin D1 gene amplification was detected in 15 (33%) and two (4%) of 46 hepatocellular carcinomas (HCC), one (10%) and 0 (0%) of 10 intrahepatic cholangiocarcinomas (ICC), one (33%) and 0 (0%) of three combined hepatocellular and cholangiocarcinomas (HCC + ICC), and nine (56%) and three (19%) of 16 metastatic lesions to the liver from colorectal adenocarcinoma (MCA), respectively. The incidence of c-myc amplification was significantly higher in MCA than in ICC (P = 0.023), and it tended to be higher in HCC than in ICC. These results indicate that the amplification of the c-myc proto-oncogene is not unusual in HCC and MCA, and its detection may have a useful diagnostic significance in differentiating ICC from MCA or HCC from ICC.