Birth weight is an established risk factor for development of childhood acute lymphoblastic leukemia (ALL); however, the biological mechanism of this correlation is unknown. Some possible mechanisms of birth weight association in childhood cancer are increased cell proliferation rate; the combination of high IGF and low IGFBP levels; maternal estrogen level; and higher iron (nutrient for cancer cells) levels in heavier babies. Birth weight increases with gestational age; therefore it is important to adjust birth weight for gestational age or use percentile of weight for gestational age or fetal growth rate in birth weight related studies. Further studies are still needed to explore biological reasons of confounder of the association between birth weight and cancer, so ultimately, preventive and therapeutic interventions can be initiated.