Objective To investigate the expression of cathepsin B (CB) in human gastric carcinoma tissue.Methods The expression of CB in human gastric tissue was studied by using monospecific polyclonal rabbit antibody raised against human liver CB for immunohistochemistry, and full length cDNA of CB for in situ hybridization and dot blot.Results CB overexpression in gastric carcinoma was found when compared with non-neoplastic gastric tissue at both mRNA and protein levels. Diffuse cytoplasmic CB staining of mRNA and protein were identified in malignant cells of 53.3% and 69.1% of gastric adenocarcinoma respectively. The increased staining of CB in malignant cells was associated with the depth of the invasiveness and growth pattern as well as metastasis of lymph nodes, but not with the histological classification. It was also found that there were the expression of CB in stromal cells of the tumor and the expression localized mainly in the endothelial cells of the microvessels which correlated with angiogenesis. Conclusion These results indicate that the expression of CB in gastric carcinoma is related to tumor progression, and leads to development of the invasive phenotype.