Thrombosis is the most frequent complication and the second cause of death in patients with overt malignant disease. Increasing evidence suggests that thrombotic episodes may also precede the diagnosis of cancer by months or years thus representing a potential marker for occult malignancy. Recently, emphasis has been given to the potential risk of cancer therapy (both surgery and chemotherapy) in enhancing the risk for thromboembolic disease. Post-operative deep vein thrombosis is indeed more frequent in patients operated for malignant diseases than for other disorders. On the other hand, both chemotherapy and hormone therapy are associated with an increased thrombotic risk, which can be prevented by low-dose oral anticoagulation. Possible contributory causes for thromboembolic disease in cancer include the capacity of tumor cells and their products to interact with platelets, clotting and fibrinolytic systems, as well as their interactions with endothelial cells and tumor-associated macrophages. Cytokine release, acute phase reaction and neovascularization may contribute, in cancer patient, to in vivo clotting activation, which is well documented by several plasmatic markers of an hypercoagulable state. Last but not least, a direct pathogenetic role of clotting activation in the progression of malignancy has been repeatedly proposed on the basis of pharmacological studies with anticoagulant/fibrinolytic drugs in experimental animals and selected clinical malignancies, as well as, lately, in genetically modified animal models (e.g. mice transgenic for PAI-1).