A 10-year-old girl was referred to our hospital with left preauricular adenopathy and gingival swelling. She was diagnosed with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) based on being positive for expressions of CD10, CD19, TdT and HLA-DR. She showed no CD20 expression at the time of diagnosis. Based on the initial diagnosis of BCP-ALL, induction chemotherapy for BCP-ALL was initiated. However, the blasts did not disappear from her peripheral blood. Bone marrow examination on day 33 identified 81.3% residual blasts with positive expressions of CD19, 20 and HLA-DR and negative CD10 and TdT expressions; these cells were morphologically and phenotypically different from those at the initial diagnosis. Based on cytogenetic studies, the final diagnosis was double-hit lymphoma/leukemia (DHL) with IgH-BCL2 and Igλ-MYC. Although dose intensive chemotherapy, including rituximab, led to complete remission, bone marrow and central nervous system relapse occurred. At relapse, blasts expressed CD10, CD19 and HLA-DR, but not CD20, findings the same as those at the onset. The patient died of the disease 44 days after cord blood transplantation with non-remission status. DHL in childhood is extremely rare and its prognosis is poor. The establishment of an effective treatment for DHL is highly anticipated.