Transient abnormal myelopoiesis is a syndrome that causes excess proliferation of immature myeloid cells and occurs in 10% to 15% of neonates with trisomy 21. Transient abnormal myelopoiesis usually resolves spontaneously but occasionally requires treatment with chemotherapy. The disorder is not typically associated with eosinophilia. We report on a neonate with trisomy 21 and transient abnormal myelopoiesis characterized by leukocytosis with marked eosinophilia. The patient required 2 cycles of cytarabine for adequate myeloproliferative control. Furthermore, this patient was subsequently also diagnosed with neurofibromatosis type 1, which has no known association with trisomy 21 or transient abnormal myelopoiesis.