We present a rare case of four immunohistochemically different primary liver cancers developing in a 54-year-old Japanese man with chronic hepatitis C. In 1989, a liver tumor had been detected at another hospital during follow-up of hepatitis C virus (HCV) infection. He was first admitted to our hospital in July 1991, when a well defined hypervascular tumor, measuring 2.5 cm in diameter was found in the S5 subsegment of the liver on computed tomography (CT); S5 subsegmentectomy was therefore performed, in July 1991. Histopathological examination revealed scirrhous hepatocellular carcinoma (SHCC). Immunohistochemical analysis showed that the tumor was negative for mouse monoclonal anti-human hepatocyte antibody (Hep), but was partially positive for a mouse monoclonal antibody specific for cytokeratin 19 (CK19). Six years after the operation, a large tumor, measuring 10 cm in diameter, was found in the S4 subsegment and a 3-cm tumor was found in the caudate lobe on CT scans. Extended left hepatic lobectomy and partial resection of the caudate lobe were performed in August 1997. Histopathological examination revealed a moderately differentiated hepatocellular carcinoma (HCC) with a trabecular pattern, an SHCC with well differentiated HCC at its periphery, and a small incidental cholangiocellular carcinoma (CCC), measuring 1 cm in diameter. The HCC and CCC showed typical immunostaining for Hep and CK19, respectively. The SHCC was positive for both Hep and CK19, showing characteristics different from those of the previously resected SHCC on immunohistochemical analysis. In conclusion, we experienced four immunohistochemically different primary liver cancers in a patient with chronic hepatitis C.