Numerous immunophenotypic features have been examined for their potential prognostic significance in predicting treatment outcome in leukaemias. These include immunophenotypic subgroups of acute lymphoblastic leukaemia (ALL) and immature acute myeloid leukaemia, expression of individual surface antigens or combined immunophenotypic features, and more recently, molecules mediating the multidrug resistance phenotype or being involved in the regulation of drug-induced apoptosis. Most previous studies investigating the prognostic significance of antigen expression in leukaemia have not used the information provided by multiparameter flow cytometry and have chosen rather arbitrary cut-off points for marker positivity. Moreover, given significant associations between immunophenotypic features and genetic abnormalities in leukaemic cells, immunophenotyping as an independent predictor of treatment outcome has been questioned. Thus, except for lineage assignment of leukaemic blasts and definition of maturational status in ALL, information provided by immunophenotyping is currently not applied to risk-classification systems or used for planning patient treatment in leukaemia. We review some of the recent findings regarding the prognostic impact of distinct immunophenotypic features in acute leukaemias and myelodysplastic syndrome.