We studied the tumor cell expression patterns of E-cadherin and matrix metalloproteinase-1, -2, -7, and -9 in a tissue microarray composed of 20 normal livers, 10 hepatocellular adenomas, 43 hepatocellular carcinomas with cirrhosis and 33 hepatocellular carcinomas without cirrhosis. Hepatocellular adenoma was characterized by the complete absence of matrix metalloproteinase-7 expression; hepatocellular carcinoma with cirrhosis was characterized by a significantly low expression of E-cadherin; and hepatocellular carcinoma without cirrhosis was characterized by low matrix metalloproteinase-9 expression. The staining intensity score of E-cadherin=3, matrix a metalloproteinase-7<1, and matrix metalloproteinase-9>or=2 can be used as the diagnostic criteria for hepatocellular adenoma and for distinguishing hepatocellular adenoma from normal, hepatocellular carcinoma with cirrhosis, and hepatocellular carcinoma without cirrhosis. E-cadherin<2 and matrix metalloproteinase-9<2 can be used for distinguishing both hepatocellular carcinoma with cirrhosis and hepatocellular carcinoma without cirrhosis from normal. Although statistically not significant, hepatocellular carcinoma without cirrhosis showed a higher E-cadherin expression and a lower matrix metalloproteinase-9 expression than hepatocellular carcinoma with cirrhosis, which could be partially responsible for the less aggressive behavior found in hepatocellular carcinoma without cirrhosis when compared with hepatocellular carcinoma with cirrhosis. These results, if confirmed in a further study of small biopsy specimens and of histologically ambiguous cases, could lead to the application of these markers in the diagnosis and differential diagnosis of hepatocellular neoplasms in our surgical pathology practice.