Patients with Philadelphia positive (Ph(+)) adult acute lymphoblastic leukaemia (ALL) have a poor prognosis. Stem cell transplantation (SCT) is increasingly being recognised as the treatment of choice in eligible patients with Ph(+)ALL, but disease-relapse remains a problem in a proportion of patients prior to and after SCT. Genetic abnormalities in addition to the Ph chromosome may influence the biology and clinical course of ALL, but there are not many studies on the potential genetic heterogeneity of adult Ph(+)ALL and clinical outcomes. Here, we report on five patients with ALL who were double Ph(+) and also had a high-hyperdiploid karyotype (Ph(+)/hyperdiploid) at diagnosis. In contrast to the presence of the Ph(+) chromosome, high-hyperdiploidy (>50 chromosomes) as the sole karyotypic abnormality in ALL is associated with a favourable clinical outcome. In our series, four patients with a Ph(+)/hyperdiploid karyotype achieved a cytogenetic remission after induction chemotherapy and proceeded to stem cell transplantation (SCT). The fifth had five subclones including Ph(+)/hyperdiploid, as well as those that were only Ph(+); the latter emerged as the dominant clone after induction therapy and the patient died of disease-relapse. Of the patients who underwent SCT, only one relapsed, but achieved a durable remission with donor lymphocyte infusions. Thus, it is conceivable that the presence of high-hyperdiploidy as an additional karyotypic abnormality may confer a better prognosis to Ph(+)ALL, presumably by altering the kinetics of Ph(+) neoplastic cells. We have discussed these results in the context of recent studies on the significance of high-hyperdiploidy in Ph(+) adult ALL.