Although severe thrombocytopenia has been reported among children with iron deficiency anemia, the presence of both anemia and thrombocytopenia can suggest serious or malignant bone marrow dysfunction, requiring further work-up. This paper reviews the management and outcomes of patients with the diagnosis of iron deficiency anemia presenting with severe thrombocytopenia. The authors present 4 pediatric patients with iron deficiency anemia and severe thrombocytopenia at initial presentation. Charts were reviewed after approval by the institutional review boards at both St. Jude Children's Research Hospital and LeBonheur Children's Medical Center in Memphis, Tennessee. All 4 patients' hemoglobin concentrations and platelet counts normalized within 1 to 3 weeks of initiating iron supplementation, suggesting that in such patients iron supplementation can obviate the need for invasive diagnostic procedures. In addition, these patients all had a platelet "overshoot" phenomenon during iron therapy prior to normalization of platelet counts, the mechanism of which is still unknown. The literature exploring the mechanism behind the current clinical findings is reviewed.