Heparin is a familiar anticoagulant drug with properties that may impede tumor growth; it modifies properties of cells that contribute to malignant dissemination such as angiogenesis, growth factor and protease activity, immune function, proliferation, and gene expression. Heparin has antitumor effects in animal models of malignancy, and studies in human malignancy show improved cancer outcome with heparin treatment. Meta-analyses comparing unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) for treatment of deep-vein thrombosis have shown apparent substantial improvement in cancer outcome in the subset of patients with malignancy who were randomly assigned to receive LMWH. This experience, together with the favorable pharmacokinetic properties of LMWH, provides a rationale for prospective clinical trials of LMWH in patients with cancer. Such trials should provide (a) definitive data on possible antitumor effects of this treatment, (b) insight into possible heterogeneous responses to heparin treatment among different histological types and stages of malignancy, and (c) a setting for exploring mechanisms of antineoplastic effect in human malignancy.