Neither histologic nor clinical staging reliably correlates with patient survival or the time course of tumor metastatic spread. There is no general biologic tumor marker which is able to distinguish those patients with microscopic residual cancer who may benefit from adjuvant anticancer treatment from those patients cured by their primary treatment who do not require additional anticancer therapy. Our data suggest that tumor activation and inhibition of fibrinolysis arc related to the likelihood of tumor spread. Calculation of mean activation/inhibition ratios (A/I ratios) in groups of tumors with and without metastatic spread demonstrated a statistically significant difference between their respective A/I ratios (p < 0.001). In addition, the mean activation/inhibition ratios for secondary or “metastatic” lesions were significantly different from the mean activation/inhibition ratios of the original tumors from which they metastasized (p < 0.001). Therefore, tumor activation/inhibition ratios would appear to have clinical reliability as biologic markers for the presence or absence of tumor metastases. These data may have important therapeutic implications that would permit the use of activation/inhibition ratios as a biologic marker for the presence or absence of tumor spread at the time of primary surgical excision of the tumor. These observations warrant further investigation into the mechanisms of tumor interaction with the fibrinolytic system.