The accurate identification of chromosomal abnormalities in patients with leukemia is essential for diagnosis and treatment assignment. Recent technical improvements in the detection of such aberrations have demonstrated that the previously unrecognized chromosomal translocation t(12;21) is the most prevalent structural aberration in childhood acute lymphoblastic leukemia. Both genes involved, translocation ets like gene (or ETV6) on chromosome 12 and acute myeloid leukemia 1 gene (or CBF alpha) on chromosome 21 had been identified for several years previously, which facilitated the rapid development of molecular diagnostic assays and their implementation in therapy trials. Although first described less than four years ago, the TEL/AML1 story is an excellent example of how close collaboration between physicians and molecular biologists is mandatory for achieving general insights into the molecular pathogenesis of leukemia and for further improvements in diagnosis and in monitoring response to chemotherapy.