Others have suggested that CD117, or an immunophenotypic profile including CD117, can serve as surrogate for FLT3 mutation in T acute lymphoblastic leukemia (ALL), thereby guiding targeted therapy. We report the results of flow cytometry immunophenotypic analysis in 42 cases of T-ALL and T/myeloid acute leukemia also assessed for FLT3 mutation. CD117 was expressed in 21 (50%), and FLT3 was mutated in 8 cases (19%; 1 T-ALL and 7 T/myeloid). FLT3-mutated cases were terminal deoxynucleotidyl transferase (TdT)+/CD2+ (7/8), cytoplasmic CD3+/CD5+ (5/8), CD7+/CD13+/CD15+ (4/6), CD33+ (4/8), CD34+, and CD117+ (bright). Cytochemistry showed myeloperoxidase-positive cells in all T/myeloid acute leukemias (3%-50%). We conclude that FLT3 mutation is rare in T-ALL, and its presence supports T/myeloid lineage. CD117 expression alone is sensitive but not specific for FLT3 mutation. The immunophenotypic profile of TdT, CD7, CD13, CD34, and CD117 (bright) is helpful for predicting FLT3 mutation, with a sensitivity of 100% and specificity of 94%.