Systemic mastocytosis (SM) with associated clonal nonmast cell lineage disease is seen in up to 20% cases of SM. SM is uncommon in the pediatric population. T (8; 21) (q22; q22) is a good prognostic factor in acute myeloid leukemia (AML). However, the presence of SM confers poor prognosis in t (8; 21) (q22; q22) associated AML. We report the case of a child with t (8; 21) (q22; q22) associated AML with SM and her minimal residual disease status over the course of her treatment. In our case, the abnormal mast cells, showing co-expression of CD25 and CD2, persisted even after the marrow showed no evidence of residual AML.