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Here we report a 3-year-old boy with myelomastocytic leukemia. The patient presented with fatigue and right eye proptosis. Bone marrow revealed acute myeloid leukemia with t(8;21) and trisomy 8. Induction therapy produced marked reduction in marrow myeloblasts with the emergence of 13% atypical mast cells. These cells were subsequently identified in retrospect in the diagnostic marrow consistent with myelomastocytic leukemia. His clinical course was notable for the difficulty in the eradication of the leukemic process and resembled that of adults with systemic mastocytosis with associated hematologic non-mast cell lineage disease. To the best of our knowledge, this is the youngest individual reported. The implications of mast cell lineage involvement in acute myeloid leukemia are reviewed.