Fluorescence in situ hybridization (FISH) provides one of the few ways of analysing the genotype of individual cells, an important consideration for mixed cell populations such as those found in leukaemia. A more sophisticated variation combines fluorescence immunophenotyping and FISH for specific leukaemia-associated chromosome rearrangements. Combined immunophenotyping and FISH is a powerful tool to identify the cell lineage in which the leukaemia-specific chromosome rearrangement occurs and has been used to identify putative pre-leukaemic cells in normal cord blood. Another valuable FISH-based research technique is multi-fluor FISH (M-FISH). This multicolour approach is effectively a molecular karyotype of individual cells and has a range of applications, from chromosome breakage studies and characterising mouse models of leukaemia, to providing a perfect complementary approach to the emerging genomic microarray technologies.