The interphotoreceptor retinoid-binding protein (IRBP) coding gene has been used with success for the large-scale phylogeny of mammals. However, its phylogenetic worth had not been explored in Actinopterygians. We explored the evolution of the structure of the gene and compared the structure predicted from known sequences with that of a basal vertebrate lineage, the sea lamprey Petromyzon marinus. This sequence is described here for the first time. The structure made up of four tandem repeats (or modules) arranged in a single gene, as present in Chondrichthyes (sharks and rays) and tetrapods, is also present in sea lamprey. In teleosts, one to two paralogous copies of IRBP gene have been identified depending on the genomes. When the sequences from all modules for a wide sampling of vertebrates are compared and analyzed, all sequences previously assigned to a particular module appear to be clustered together, suggesting that the divergence among modules is older than the split between lampreys and other vertebrates. Finally, 92 acanthomorph teleosts were sequenced for the partial module 1 of the gene 2 (713 bp) to assess for the first time the use of this marker for the systematic studies of the Teleostei. The partial sequence is slightly more variable than other markers currently used for this group, and the resulting trees from our sequences recover most of the clades described in the recent molecular multi-marker studies of the Acanthomorpha. We recommend the use of partial sequences from the IRBP gene 2 as a marker for phylogenetic inference in teleosts.