B-lymphoblastic leukemia (B-ALL) in children is characterized by recurrent chromosomal rearrangements that mostly have prognostic value. MYC rearrangements (MYC-r), typically associated with Burkitt lymphoma or mature B-cell neoplasms are infrequent in B-ALL. We report here a unique case of childhood B-ALL with concurrent MYC-r with a non-IG partner and a cryptic t(12
21). Leukemic cells had lymphoblastic morphology. Immunophenotypically, leukemic blasts were CD10 (+, slightly bright), CD15 (few +), CD19 (+), CD20 (+, partial), CD22 (+), CD34 (-), CD38 (+, slightly variably), CD45 (+, partial), cytoplasmic CD79a (+), HLA-DR (+), surface Ig (-), MPO (-), and TdT (+, partially). This immunophenotype was consistent with B-ALL. Cytogenetically, the karyotype was complex including a t(4
8)(q31
q24), and FISH analysis showed MYC-r, ETV6::RUNX1 and loss of ETV6 allele. The patient has been in complete remission for 11 years following the diagnosis. We reviewed cases of B-ALL with double leukemogenic alterations and MYC-r with non-IG partners to understand the clinical outcome in these rare patients.