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Central nervous system (CNS) chloromas are an exceedingly rare presentation of CNS relapse in acute lymphoblastic leukemia (ALL). We report a relapsed ALL patient who presented with 2 separate chloromas and cerebrospinal fluid lymphoblastocytosis, and outline a treatment plan of systemic chemotherapy and CNS-directed radiation therapy. A review of the literature indicates that multiagent chemotherapy combined with CNS radiotherapy is effective, with hematopoietic stem cell transplantation used in half of reported cases. We conclude that intensive systemic multiagent chemotherapy with CNS-directed radiation therapy can be successfully used to treat relapsed pediatric ALL with CNS lymphoblastic chloroma.