In patients with malignant diseases, despite a direct relationship between the level of platelet count and bleeding episodes, it is evident that the risk of bleeding depends not only on the platelet count, but also on the underlying disease, the use of drugs interfering with platelet function and complications such as fever and infection or the presence of coagulation defects. As a consequence, it is not only the absolute platelet count, but rather the number of functional platelets that is important for the prevention of bleeding. As for Prophylaxis of hemorrhagic risk in these setting of patients, studies have now convincingly demonstrated that a 10,000/microL threshold for prophylactic platelet transfusion is safe and effective in uncomplicated thrombocytopenic patients. However, a threshold of 20,000/microL must be considered only for patients with high fever, hyperleukocytosis, coagulation abnormalities or who necessitate of invasive procedure. Moreover, as suggested by the clinical practice guidelines of the American Society of Clinical Oncology, a threshold of 20,000/microL must be considered for patients receiving aggressive therapy for bladder tumors and for those with demonstrated necrotic tumors.