The progressive availability of more sophisticated technologies has over the last few years allowed a more precise definition of the biological properties of acute leukaemia cells. This, in turn, has enabled to recognize the ontogeny of practically all cases, with particular emphasis to acute lymphoblastic leukaemia, the lineage affiliation of which had, for many years remained uncertain in over half of the cases. Here, we shall review the main achievements, obtained with extensive immunotyping coupled to the use of probes for the immunoglobulin and T-cell receptor genes, which have led to these important clinico-biological acquisitions, and discuss specific situations in which this combined phenotypic and genotypic approach (as well as response to cloned growth factors) may be of particular value.