A 2-year-old girl with TCF3-ZNF384 re-arranged standard-risk B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) showed an apparent lineage-switch to predominantly myeloid blasts following 7-days of corticosteroid therapy. ZNF384-re-arranged leukemias are increasingly recognized to present either as mixed-phenotype acute leukemia or as BCP-ALL with pro-B immunophenotype. Lineage switch is a rare phenomenon described at relapse or following CAR-T-cell therapy previously mostly in KMT2A re-arranged leukemias; and now, also in ZNF384-rearranged patients. It is previously unreported in any patient after pre-phase corticosteroid therapy. Hematologists should be aware of this distinct emerging entity among leukemias with multi-lineage differentiation potential.