The interactions between components of the hemostatic system and cancer cells are multifaceted. Strong clinical evidence is accumulating on the prothrombotic tendency of cancer patients, which is enhanced by anticancer therapy, such as surgery and chemotherapy. The mechanisms of thrombus promotion in malignancy include some general responses of the host to the tumor (acute phase, inflammation, angiogenesis) and specific interactions of tumor cells with the clotting/fibrinolysis systems and with blood (leukocytes, platelets) or vascular cells. It is at present difficult to rank the relative weight of these multiple interactions on the basis of the well-recognized clinical evidence of enhanced thrombotic episodes in tumor patients. In any case, the mechanisms explored so far offer a sound experimental basis for prevention/treatment of thrombosis in tumor patients and leave open the possibility that some antithrombotic strategies may also affect the processes of tumor growth and dissemination.