Expression of the sialyl Lewis(x) antigen, a cell adhesion molecule, was studied immunohistochemically in patients with hepatocellular carcinomas.Fifty-six patients who underwent curative hepatic resections from July 1984 to October 1990 were studied.Hepatocellular staining patterns of the sialyl Lewis(x) in cancerous or noncancerous regions were divided into the three categories of high grade (HG), medium grade (MG), and low grade (LG). In cancerous regions, HG:54% (30/56); MG:13% (7/56); LG:34% (19/56). In noncancerous regions, HG: 86% (48/56), MG:4% (2/56), LG:11% (6/56). Patients with LG or MG sialyl Lewis(x) expression in cancerous regions had vascular invasion more frequently, and larger maximum diameters than HG patients, both with statistical significance (p<0.01, p<0.05, respectively). The 20 cases in which the expression of sialyl Lewis(x) in cancerous regions was downgraded compared with noncancerous regions (from HG in noncancerous regions to MG or LG in cancerous regions; from MG in noncancerous regions to LG in cancerous regions), also had vascular invasion significantly more frequently than the other 36 cases (p<0.02).These results lead us to speculate that the diminishing change of hepatocellular sialyl Lewis(x) expression with malignant transformation, or the small amounts of hepatocellular sialyl Lewis(x) expression in cancerous regions, are related to tumor spread of hepatocellular carcinoma.