The introduction of routine molecular cytogenetic assays enabled us to reveal hitherto unknown genetic disorders of childhood acute leukemias. Of special interest is the recognition of those rare cytogenetic mutations of negative prognostic value, which are associated with well-known markers of good prognosis. In our present study we review a novel cytogenetic mutation typical for childhood B-cell ALL, the intrachromosomal amplification of chromosome 21, which requires high-risk therapy irrespective of other risk factors, and which is associated with a cryptic 12;21 translocation of good prognostic value.