The hemostatic system is involved in multiple interactions with transformed cells that progress from a dormant, non-vascularized tumor to highly metastatic phenotypes. Oncogenic transformations up regulate not only the initiator of the coagulation cascade, tissue factor (TF), but also induce other molecules that are required for TF's direct cell signaling activity, including the protease activated receptor (PAR) 2 and factor VIIa. TF-dependent signaling is a major driver for primary tumor progression, whereas TF-initiated coagulation and other components of the hemostatic system support metastasis. Basic research continues to identify pivotal molecular interactions in these processes and provides potential leads for targeting specific tumor promoting pathways associated with hemostasis and thrombosis.