Pathogenesis of the prothrombotic state of cancer patients is due, at least in part, to the ability of cancer cells to activate the coagulation system. Several complex and not fully recognized interactions between the malignant cell and the clotting system promote a shift in the haemostatic balance compared with a procoagulant state. Tumour cells possess the capacity to interact with the haemostatic system in multiple ways. The principal mechanisms include the expression of haemostatic proteins by tumour cells, the production of inflammatory cytokines by tumour and/or host cells, and the direct adhesion of tumour cells to normal cells, including platelets, endothelial cells and monocytes. This chapter will summarize the prothrombotic mechanisms of tumour cells and their role in both coagulation and tumour progression. In particular, this chapter will focus on the capacity of tumour cells to promote activation of the coagulation system, and on the mechanisms by which clotting proteins may promote tumour growth and metastasis.