A 14-year-old boy with Philadelphia chromosome-positive chronic granulocytic leukaemia underwent morphologically distinctive blastic transformation on 3 separate occasions. The first was clearly lymphoblastic, the second was associated with meningeal leukaemia and was morphologically biphenotypic, expressing mixed myeloid and lymphoid features, while the third was characterised by extreme thrombocytosis and megakaryoblastic proliferation. The classical t(9:22) Philadelphia chromosome remained constant throughout the illness, but the additional cytogenetic changes that occurred with the first transformation were abolished with response to conventional therapy for lymphoblastic leukaemia. A total of 19 months of good-quality life was achieved, but on the third occasion, the boy died from intracranial haemorrhage before treatment could be initiated.