- In recent years immunophenotyping and analysis of clonal rearrangement of immunoglobulin and T-cell antigen receptor genes have proved valuable for the diagnosis and classification of leukaemia. These techniques aid in the assignment of cell lineage in cases of acute leukaemia in which the standard FAB criteria of morphology and cytochemistry do not reveal clear lymphoid or myeloid phenotype. These new techniques have also revealed that the leukaemic blasts in a sizable minority of otherwise typical cases of acute leukaemia express 'inappropriate' lineage-associated markers and have been termed mixed acute leukaemias. The spectrum of characteristics encompassed by mixed acute leukaemias ranges from fairly common cases expressing one or two inappropriate markers to the more extreme, rare cases of acute leukaemia termed 'hybrid' in which a truly scrambled picture is seen. A subgroup of these mixed cases have two distinct populations of blasts, e.g. one lymphoid and the other myeloid. These observations raise a number of issues about the cell of origin of these leukaemias and about the mechanisms controlling the developmental regulation of expression of different lineage-associated markers. In addition, accumulating evidence suggests that inappropriate expression of markers may identify sub-groups of both acute myeloid and lymphoblastic leukaemia with an inferior prognosis.