Recent studies have reported significant but inconsistent correlations between tumor cathepsin D (CD) concentration and prognosis in breast carcinoma. To investigate the tissue distribution and a prognostic utility of CD in breast carcinoma, 159 cases of T2N0M0 breast carcinoma with a minimum of 10 years' follow-up were studied for CD expression by immunohistochemistry. This group of patients was chosen for study because of current interest in prognostic markers for stage I breast carcinoma and the likelihood that there would be sufficient recurrences in this group to detect significant differences. Seventy-two carcinomas (45%) showed prominent staining of cells composing the tumor. Neoplastic cell staining for CD correlated with well-differentiated architecture, and lack of neoplastic cell CD expression correlated with high nuclear grade and the medullary carcinoma category. Stromal cell (primarily histiocyte) staining in carcinomas was the major contributor to CD expression in 67 of the 159 cases (42%). Intense intratumoral stromal cell staining correlated with absence of estrogen receptors and the medullary carcinoma subtype. There was no significant correlation between disease-free or overall survival and (a) intensity of overall staining for CD, (b) staining of carcinoma cells alone, or (c) staining of nonneoplastic cells within the region of the carcinoma. These results show that a significant proportion of CD activity detected within a tumor by immunohistochemistry may be contributed by nonneoplastic cells, and there is no significant correlation between survival and immunohistochemical detection of CD in T2N0M0 breast cancer.