As outlined in this review, patients with cancer may harbor many alterations of hemostasis. These are multifaceted and must be taken into account when trying to control hemorrhage or thrombosis in cancer patients. Often, hemorrhage or thrombosis is the final fatal event in many patients with metastatic solid tumor or hematologic malignancies. Patients with malignancy present a major clinical challenge in this new era of oncologic awareness and more aggressive care, which has led to prolonged survival for patients and a longer time frame during which these complications may develop. Therefore, these complications are occurring more commonly. It is important to realize that these alterations of hemostasis exist and must be approached in a sequential and logical manner with respect to diagnosis; only in this way can responsible, efficacious, and rational therapy be delivered to patients. By far the most common alteration of hemostasis in malignancy is that of hemorrhage associated with thrombocytopenia, either drug-induced, radiation-induced, or from bone marrow invasion. However, hemorrhage resulting from DIC is also quite common and may present as hemorrhage, thrombosis, thromboembolus, or any combination thereof. Many antineoplastic drugs and radiation therapy may lead to or significantly enhance hemorrhage in patients with malignancy. Thrombosis, also commonly seen in patients with malignancy, is often a manifestation of low-grade DIC, conspicuous as an intravascular thrombotic or thromboembolic event instead of an intravascular proteolytic (hemorrhagic) event. When suspecting this, confirmatory laboratory evidence must be sought and the patient treated appropriately. When approaching the patient with malignancy and either hemorrhage or thrombosis, all the potential defects in hemostasis must be taken into account, defined from the laboratory standpoint, and treated in as precise and logical manner as possible.