Urokinase plasminogen activator (UK-PA) is a serine protease implicated in cancer invasion and metastasis. In this investigation, patients with breast cancers containing high levels of UK-PA antigen had significantly higher risk of early disease recurrence and shorter overall survival than did patients with low levels of the protein. In univariate analysis, UK-PA was a more powerful discriminator for disease-free interval than axillary node status, tumor size, or estradiol receptor. For overall survival, UK-PA as a prognostic marker, was of similar magnitude to axillary node status but stronger than that of tumor size or estradiol receptor. In multivariate analysis, for both disease-free interval and survival, UK-PA was an independent risk factor, being independent of tumor size, axillary node status, and estradiol receptor. UK-PA appears to be a new and independent prognostic marker in breast cancer.