Apoptosis, a programmed cell death, can be observed in the tissues of viral or autoimmune hepatitis and of hepatocellular carcinoma. Fas antigen (Fas) was proposed as a protein that triggers apoptosis. To elucidate the relationship between Fas expression and its location in hepatocellular carcinoma cells, we histochemically examined Fas expression by using 25 hepatocellular carcinoma tissues and their corresponding noncancerous tissues, which were surgically obtained from the same patients. In addition, the relationship between Fas expression and apoptotic cell numbers was examined in the hematoxylin-and-eosin-stained specimens obtained from 23 of the 25 patients. Hepatocellular carcinoma tissues expressed Fas less frequently and more weakly than noncancerous tissues. The majority of noncancerous specimens expressed Fas both on the surface and in the cytoplasm, whereas the majority of hepatocellular carcinoma expressed Fas only in the cytoplasm. Apoptotic cell counts were significantly higher in Fas-expressing tissues than in Fas-negative tissues. Among Fas-expressing tissues, the counts were higher in surface Fas-expressing tissues than in tissues that expressed only cytoplasmic Fas (P < 0.01 to 0.05). Our findings indicate that the development of apoptosis in hepatocellular carcinoma tissues relates to not only Fas expression but also its location.