OBJECTIVES: No study has estimated the potential health benefits of breastfeeding on childhood leukemia using the Healthy People (HP) 2020 national goals. We estimated expected life-years (LYs) saved, lifetime medical cost-savings and productivity gained from the reduction of childhood leukemia from breastfeeding under three scenarios: a) ever breastfed, b) breastfed at 6 months, and c) breastfed at 12 months. METHODS: A total of 19,913 children aged 0-14 years diagnosed with leukemia were obtained from the 2001-2011 population-based National Program of Cancer Registries and the Surveillance, Epidemiology, and End Results Program. The survival function for an age- and sex-matched reference population was generated from US life tables. Using data generated from simulations, we calculated 1) the number of new leukemia cases prevented, 2) expected LYs saved, 3) lifetime medical cost-savings, and 4) lifetime productivity gained if the HP 2020 goals were met.  RESULTS: We estimated 52 new cases or 19.4% increase in leukemia cases prevented if the HP 2020 goal for ever breastfeeding was met. These new cases prevented were associated with 661 LYs saved, and estimated total lifetime economic cost-savings of $197.8 million. At 6 months breastfeeding duration, 102 new cases representing 52.3% increase in leukemia prevented, which accounted for 1,306 LYs saved and a total lifetime economic cost-savings of $390.8 million. At 12 months breastfeeding duration, 86 (63.7%) new leukemia cases were prevented accounting for 1,101 LYs saved and total lifetime economic cost-savings of $329.5 million. All estimates were statistically significantly different between HP 2020 (target year) and HP 2006 (baseline year) at p<0.001. CONCLUSIONS: Meeting the HP 2020 goals on breastfeeding rates are likely to prevent a substantial number of new leukemia cases, save a substantial number of LYs, and economic costs to society. These findings suggest that efforts to promote and support breastfeeding may be effective in reducing the childhood leukemia.