B-lymphoblastic leukemia/lymphoma (B-ALL) is the most prevalent childhood malignancy, with improved survival rates attributed to advances in diagnosis and treatment. Herein, we present a case of B-ALL in a 6-year-old female who presented with clinical symptoms of leukemia, including weight loss, fever, and lymphadenopathy. Molecular and cytogenetics study revealed a t(1;22) resulting in an EWSR1::PBX1 fusion. This case highlights diagnostic and prognostic implications of this recently recognized distinct EWSR1 entity.
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