A 5-year-old male child was diagnosed with interdigitating dendritic cell sarcoma (IDCS) during his maintenance therapy for B-cell precursor acute lymphoblastic leukemia (B-ALL). Multiplex lymph node involvements of the neck were found by positron emission tomography CT (PET-CT). Treatments, including surgical and chemotherapy, resulted in complete remission. Four years later, systemic bone infiltration was discovered. Surgical resection of the IV rib and intensive chemotherapy led to a complete morphological remission, and allogeneic bone marrow transplantation was performed. Comprehensive genomic profiling of the formalin fixed the tumor tissue, and the cryopreserved leukemic cells revealed several common alterations and divergent clonal evolution with a novel MAP2K1 mutation of the IDCS, which is responsible for the trans-differentiation of the common lymphoid-committed tumor progenitor.