This review is based on pediatric reports (- January 2004) on the presence of symptomatic thrombosis in children with hematologic malignancies, mainly acute lymphoblastic leukemia, treated with different treatment protocols and associated with acquired and inherited prothrombotic risk factors (factor V G1691A, factor G20210A, MTHFR C677T genotypes, protein C, protein S, antithrombin, elevated levels of lipoprotein(a), and homocysteine). The interactions of treatment modalities, study designs, ethnical backgrounds and associated central lines are discussed. Based on the data presented here, we suggest the use of prednisone and E. coli asparaginase concomitantly administered in a leukemic patient suffering a prothrombotic risk factor to be responsible for the onset of venous thrombosis in the majority of cases. In addition, primary preventive anticoagulant/antithrombotic strategies are discussed.