The urokinase-type plasminogen activator receptor (uPAR, CD87) plays a central role in the plasminogen activation cascade, which participates in extracellular matrix degradation, cell migration and invasion. Here we performed a comprehensive immmunohistochemical evaluation of uPAR expression in primary tumor cells, tumor-surrounding fibroblasts, lymph node metastases and micrometastatic cells in bone marrow of patients with breast carcinomas at the time of primary diagnosis. Variable degrees of uPAR staining of tumor cells were observed in 84 of 93 (90%) carcinomas, whereas intratumoral fibroblasts were uPAR-positive in 70 (75%) carcinomas. The fraction of uPAR-positive primary tumor cells but not fibroblasts was positively correlated with the presence of tumor cells in bone marrow (p = 0.037), whereas no correlation with lymph node metastasis was found. Immunophenotyping of bone marrow and lymph node specimens revealed expression of uPAR on metastatic tumor cells in 10 of 13 and 22 of 23 cases, respectively. Direct comparison to the autologous primary tumor cells showed different uPAR staining scores in most patients with evidence for both up- and downregulation of uPAR on metastatic cells. Our results indicate that uPAR plays an active role in breast cancer metastasis and may therefore be a promising target for new biologic therapies. © 2003 Wiley-Liss, Inc.