TF expression is a hallmark of cancer progression. The procoagulant functions of TF that lead to thrombin generation are critically important to support metastasis, in part through the generation of fibrin that assures prolonged arrest of tumor cells in target organs. In addition, the coagulation initiation complex, i.e. TF-VIIa-Xa, generates autocrine cell signaling though protease activated receptors. A cooperation of the TF cytoplasmic domain with protease signaling may explain the diverse contributions of TF to metastasis and angiogenesis.