Lung bronchioalveolar carcinomas (BACs) are noninvasive tumors showing lepidic growth and excellent prognosis, whereas all the other variants of adenocarcinoma are invasive tumors with a worse prognosis. The identification of minimal invasive foci in adenocarcinoma, therefore, is of prognostic relevance. A series of 68 pulmonary tumors, including 40 acinar/papillary adenocarcinomas, 18 adenocarcinomas of the mixed subtype, and 10 BACs was tested by immunohistochemical analysis for cathepsin K expression, a proteinase involved in bone and extracellular matrix remodeling. Cathepsin K was produced by epithelial tumor cells in most invasive adenocarcinomas and, interestingly, by macrophages and fibroblasts in the stroma of invasive adenocarcinomas but not of BACs (P < .001). Our findings suggest pathogenetic implications of cathepsin K in the mechanisms of tumor invasiveness in lung carcinoma; in addition, cathepsin K immunodetection may be a valuable adjunct in the correct classification of pulmonary adenocarcinomas, especially in small sclerosing BACs and mixed adenocarcinoma subtypes with minimal infiltrative growth.