This brief report describes the importance of close discussion between clinicians and scientists and progress in leukaemia genetic work-up to deliver optimal treatment to a girl with 2 episodes of childhood Acute Lymphoblastic Leukaemia. At initial presentation, limited cytogenetic analyses did not identify any recurrent genetic abnormalities and the patient was subsequently treated according to NCI risk criteria on regimen A of UKALL2003. Nine years later, she presented with low hypodiploid ALL which was associated with genetically confirmed Li-Fraumeni Syndrome. Genetic backtracking established late relapse of the initial ALL which was instrumental in informing treatment decisions.