Vascular endothelial growth factor (VEGF) is one of the most potent and specific positive regulators involved in angiogenesis. The activity of VEGF is mediated by interaction with high affinity class III receptor tyrosine kinases (RTKs), expressed on most endothelial cells, which are VEGFR-1 (FLT-1), VEGFR-2 (KDR) and VEGFR-3 (FLT-4).VEGF and its receptors may play a very important role not only in angiogenesis but also in leukemogenesis. Their expression on leukemic cells may elucidate its role as an autocrine promoter of malignant cell proliferation in acute leukemia whether myeloblastic or lymphoblastic and in other hematologic malignancies as they trigger proliferation, survival and migration of malignant hematopoietic cells. Their expression may have clinical relevance and important role as risk and prognostic factors in acute leukemia. They may be useful as predictive test for treatment outcome in acute leukemia patients.