The standard methods to diagnose leukemia are cytomorphology and, in some cases, histology, which both are supplemented by cytochemistry and multiparameter immunophenotyping. Cytogenetics, fluorescence in situ hybridisation (FISH), and polymerase chain reaction (PCR) assays add important information and allow comprehensive diagnosis of well-defined subentities today. In the clinic, better understanding of the course of distinct, biologically defined disease subtypes is the basis for a selection of specific therapeutic approaches. As knowledge on deregulated pathways in leukemia accelerates the development of new therapeutics, a detailed and comprehensive diagnostic tool is required. The microarray technology that quantifies gene expression intensities of thousands of genes in a single analysis has the potential to become essential for the molecular classification of leukemias. Microarrays may be used routinely for diagnostic purposes in the near future. Gene expression profiling should also lead to the detection of new biological and clinically relevant subtypes in leukemia and therefore guide therapeutic decisions.