Mixed phenotype acute leukemia (MPAL) is a rare type of acute leukemia where blasts present phenotypes from more than one lineage. A poor prognostic has been associated with this disease and limited data is currently available to guide the choice of therapy. Regarding FLT3-positive MPAL, only one case treated with midostaurin has been published to date. Here, we report the successful use of midostaurin to treat three FLT3-positive MPAL T/myeloid and B/myeloid patients. Midostaurin was successfully added to intensive induction (two patients) and consolidation chemotherapy (three patients) without significant adverse events requiring a dose adjustment or discontinuation. The therapy received resulted in complete remission for two patients and complete remission with an incomplete hematologic recovery for the third. All patients proceeded to HSCT and stayed in remission after extended follow-up respectively at 28, 31 and 11 months later. These results suggest that the addition of midostaurin during induction and consolidation therapy may represent a treatment option for FLT3-positive MPAL.