Plasminogen activator is a protease existing in two forms known as tissue-type and urokinase-type plasminogen activator. In this investigation, patients with breast cancers containing high levels of the tissue-type enzyme had a significantly longer disease-free interval and survival compared with patients with low levels of the enzyme. For the disease-free interval, the effect of tissue-type plasminogen activator was independent of tumor stage, grade, axillary node involvement, and estradiol receptor status. It is concluded that tissue-type plasminogen activator is a new prognostic marker in breast cancer.