The management of patients with chronic myeloid leukemia (CML) in advanced phases is challenging and requires the consideration of different treatment approaches, including targeted therapy with tyrosine kinase inhibitors, cytotoxic chemotherapy, and allogeneic stem cell transplantation. Here, we present the case of a patient with CML in mixed phenotype blast phase illustrating the integration of these strategies and demonstrating the need for close monitoring of treatment response in order to individually adjust treatment regimens.