Recruitment of myeloid cells by TF-induced coagulation promotes metastasis. TF expressed in cancer cells triggers the coagulation cascade that results in thrombin formation, platelet activation, and fibrin deposition. The clots formed on the tumor cells serve to recruit a subset of monocytes/macrophages that are essential for in vivo tumor cell survival and for the establishment of a premetastatic niche. Prevention of clot formation, by inhibition of either TF (with TFPI) or thrombin (with hirudin), results in a decreased recruitment of monocytes/macrophages that perturbs tumor cell survival and the establishment of a premetastatic niche. Impairment of monocyte/macrophage function, in mice depleted of CD11b cells or in Mac1 KO mice, leads to the same consequences, despite the formation of clots on the tumor cells. Thus, TF and the monocyes/macrophages it recruits are potentially interesting targets in the treatment and prophylaxis of metastases.