Juvenile myelomonocytic leukemia (JMML) is a rare childhood neoplasm with features characteristic of both myelodysplastic and myeloproliferative disorders. Children with JMML typically present with marked splenomegaly and hepatomegaly and varying degrees of lymphadenopathy, pallor, and skin rash. The peripheral blood usually show leukocytosis, absolute monocytosis, often with dysplastic features, anemia, and thrombocytopenia. While the bone marrow findings are less specific, hypercellularity due to myelomonocytic proliferation, mild dysplasia, and a reduced number of megakaryocytes are usually present. The hallmark of JMML is hypersensitivity of marrow progenitors to granulocyte-monocyte colony stimulating factor (GM-CSF) in vitro. Recent studies have shown that this abnormal proliferation is due to an aberrant signal transduction resulting from mutations in components of the RAS-signaling pathway. JMML is an aggressive neoplasm and, while hematopoietic stem cell transplantation is currently the only curative option, there is an unacceptably high relapse rate after transplant.