Gene expression profiling using DNA microarrays represents a major advance in the diagnosis of haematological malignancies; it enables the analysis of RNA expression by clonal populations of leukaemia and lymphoma cells on a genome-wide scale. Currently, flow cytometric analysis of differentiation-linked surface antigens expressed by malignant cells is essential for the accurate diagnosis and optimal therapeutic planning for patients with leukaemias and lymphomas. Given the astonishing pace of research in microarray technology, a key question for the haematopathologist is: will gene expression profiling using DNA microarrays replace immunophenotyping, or will these two technologies evolve together as complementary approaches to improve diagnosis and therapy? In this chapter, we review the technical advantages and pitfalls of each of these two approaches and provide an assessment of their differences and potentially synergistic applications.