CD10 is a cell surface neutral endopeptidase that is not consistently expressed in the stromal cells of the normal breast. Expression of CD10 is sometimes observed in the stromal cells of invasive ductal carcinoma, but its clinical significance has never been studied. Immunohistochemical examination of CD10 was performed in 123 cases of breast cancer. The median follow-up period of all patients was 8.0 years, and univariate and multivariate analyses were performed to evaluate the prognostic significance of stromal CD10 expression. There was no staining in the stromal cells of 13 non-invasive ductal carcinomas or normal breast tissue. Of 110 invasive ductal carcinomas, 20 cases (18%) in which more than 10% of the stromal cells stained positive throughout the cancer tissue were judged "positive". The frequency of positive stromal staining was significantly higher in the cases with axillary lymph-node metastasis ( P=0.038), but there were no correlations between stromal CD10 expression and age, tumor size, histologic grade, or clinical stage. The patients whose tumors contained CD10-positive stromal cells had a shorter metastasis-free interval ( P=0.0008). Univariate analysis demonstrated that patients with lymph-node metastasis also had a significantly shorter metastasis-free interval (metastasis vs no metastasis; P=0.0318). In the multivariate analysis, only CD10 remained a significant predictor for time to recurrence ( P=0.0059), and CD10 was the single significant prognostic factor for overall survival in the univariate analysis ( P=0.0021). These results suggest that stromal expression of CD10 in breast cancer is an important novel prognostic factor.