The differentiation of cells in the vertebrate skeleton is controlled by a precise genetic program. One crucial regulatory gene in the pathway encodes the transcription factor Runx2, which in mouse is required for differentiation of all osteoblasts and the proper development of a subset of hypertrophic chondrocytes. To explore the differentiation of skeletogenic cells in the model organism zebrafish (Danio rerio), we have identified two orthologues of the mammalian gene, runx2a and runx2b. Both genes share sequence homology and gene structure with the mammalian genes, and map to regions of the zebrafish genome displaying conserved synteny with the region where the human gene is localized. While both genes are expressed in developing skeletal elements, they show evidence of partial divergence in expression pattern, possibly explaining why both orthologues have been retained through teleost evolution.