Cancer stem cells can escape therapeutic kill by adopting a quiescent or dormant state. The reversibility of this condition provides the potential for later recurrence or relapse, potentially many years later. We describe the genomics of a rare case of childhood BCR-ABL1 positive, B cell precursor acute lymphoblastic leukaemia (ALL) that relapsed, with an AML immunophenotype, 22 years after the initial diagnosis, sustained remission and presumed cure. The primary and relapsed leukaemias shared the identical BCR-ABL1 fusion genomic sequence and two identical immunoglobulin gene rearrangements, indicating that the relapse was derivative of the founding clone. All other mutational changes (SNV, CNAs) were distinct in diagnostic or relapse samples. These data provide unambiguous evidence that leukaemia-propagating cells, most probably pre-leukaemic stem cells, can remain covert and silent but potentially reactivatable for more than two decades.Leukemia accepted article preview online, 28 May 2015. doi:10.1038/leu.2015.132.