The principal initiator of coagulation, Tissue Factor (TF) has now emerged as a critical key player in oncogenic events. TF regulates tumor growth through processes such as anti-apoptosis, tumor angiogenesis and metastasis in various solid tumors such as colorectal carcinoma, glioma and breast tumors. In the last few years it has become clear that these effects are not, or partially, attributable to activation of coagulation. Rather, activation of cellular receptors, by the binary TF:FVIIa complex, the ternary TF:FVIIa:FXa complex or by thrombin, results in intracellular signaling and altered cell behaviour. In this review, the role of TF in complex with FVIIa or FVIIa:FXa as well as the role of the Tissue Factor Pathway Inhibitor in cancer will be discussed.