Production of cathepsin B by tumor cells has been linked to metastatic potential in several experimental models. Sections of 95 primary lung adenocarcinomas were examined for expression of cathepsin B using a standard avidin-biotin immunohistochemical technique. Staining for cathepsin B was observed in 22.1% of all cases and 28.0% of those of the Clara cell type. In Clara cell adenocarcinomas, cathepsin B expression correlated with positive lymph node status, presence of distant metastases, and poor prognosis (P < 0.05). However, no correlation with clinical outcome was observed in other cell types. Our data suggest that cathepsin B may be involved in invasion and metastasis in Clara cell lung adenocarcinoma.