Recurrent fusion genes (FGs) with clinical significances in leukemias are mainly mutually exclusive, and the coexistence of different FGs has been rarely reported. In this study, we retrospectively analyzed the incidence, genetic characteristics, and prognosis of leukemias with concurrent pathogenic FGs, which commonly reported in hematological malignancies in 8226 leukemia patients. A total of 25 patients with coexistence of double FGs were identified, accounting for 0.30% of all cases enrolled. More than half of the cases (14/25, 56%) were diagnosed as chronic myeloid leukemia in accelerated or blast phase, another six and five cases were acute myeloid leukemia and acute lymphocytic leukemia, respectively. Most cases (20/25, 80%) carried constitutively activated tyrosine kinases FGs (BCR-ABL1 or ETV6-PDGFRB) and transcription factors associated FGs simultaneously. Of the 11 patients with contemporaneous karyotype, 5 (45%) showed visible chromosomal abnormalities corresponding to both FGs. The concurrency of FGs was often associated with disease progressions. The prognosis was pessimistic for patients with concurrent FGs, even with the combination of targeted therapy and chemotherapy. Performing allogeneic hematopoietic stem cell transplantation as soon as possible after complete remission can ameliorate the dismal prognosis.