Heparin was isolated from the liver and heart in 1916. Heparin was demonstrated as an anticoagulant in the presence of heparin-cofactor, a plasma component. Over years many heparin molecules have been manufactured due to their anti-tumor properties. Heparin sulfate, an essential component of the extracellular matrix when degraded by heparanase secreted by tumor cells has shown to increase tumor invasiveness. The anti-angiogenic properties of heparin are due to its effect on decreasing fibrin level and inhibition of thrombin formation. Natural killer (NK) cells destroy circulating tumor cells. The anti-tumor properties of heparin have been demonstrated in various studies. Among various forms of heparin, butanoylated heparin has the lowest anticoagulation strength but much stronger anti-tumor activity compared with UFH at higher doses. The anti-tumor effects between LMWH and butanoylated heparin are yet to be compared.