AML with RUNX1::RUNX1T1 fusion represents another paradigm of how a single cytogenetic abnormality of t(8;21)(q22;q22) suffices in delineating a distinct leukemia subtype, in terms of morphology, immunophenotype, association with recurrent cooperating mutations, and favorable clinical outcomes. The gene discussed is RUNX1; the disease is acute myeloid leukemia.