Comparative genomics offers a powerful opportunity to identify the considerable synteny and thereby gain an understanding of how the genome has been remodeled during evolution. Using the chicken prolactin receptor (cPRLR) and growth hormone receptor (cGHR) genes as seed orthologs, 13 genes were mapped on the chicken chromosome Z and the synteny compared with those in other vertebrates including human, chimpanzee, rat, mouse, and zebrafish. Strikingly, highly conserved syntenies were noticed among the 4 mammalian species and chicken. However, changes in arrangement and orientation of genes within the conserved region were found among these species, indicating that intrachromosomal inversions had occurred more frequently than interchromosomal translocations since the divergence of birds and mammals. Although zebrafish PRLR and GHR were localized on 2 distinct linkage groups (LG21 and LG8), 2 syntenies on LG21 and LG5 were consistently observed in all species examined. The current result suggested that the 2 syntenies were extremely conserved during vertebrate genome evolution, and most large gene syntenies including the PRLR-GHR region were formed after teleosts.