We report a case of isolated extramedullary leukemia relapse in the breast of an adolescent girl. A 13-year-old girl with acute lymphoblastic leukemia in remission, post-chemotherapy and unrelated cord blood transplant, presented with a breast lump. US and mammography demonstrated a large hypervascular heterogeneous mass. Examination of tissue provided by US-guided core biopsy confirmed focal leukemic relapse. US is a commonly used diagnostic tool in children and adolescents with a breast mass, for both characterization and guided biopsy.