In mammals the HOX network consists of 39 genes which encode master regulators of developmental processes including hematopoiesis. Many of the chromosomal translocations associated with acute leukemias involve HOX genes directly or some of their regulatory factors, e.g., mixed lineage leukaemia (MLL), leading to inappropriate expression of certain subsets of the genes. Evolutionarily, the HOX genes are thought to have arisen by duplication and divergence from a primordial gene. Consequently, they exhibit a high degree of sequence similarity, particularly in the homeobox domain. HOX gene expression, the HOXOME, can be quantified by real-time quantitative PCR (RQ-PCR) using carefully selected reagents. In practice, an RQ-PCR platform based on Taqman probe chemistry has proved valuable for the precise measurement of individual human and murine HOX genes with a high degree of specificity, over a wide dynamic range. Defining the roles for HOX in hematopoiesis should help to elucidate the mechanisms of deregulation in leukemia and eventually identify targets for therapeutic intervention.