Stearoyl-CoA-desaturases (SCDs) are key enzymes of fatty acid biosynthesis whose regulation underpins responses to dietary, thermal and hormonal treatment. Although 2 isoforms are known to exist in the common carp and human, and 4 in mouse, respectively, there is no coherent view on how this gene family evolved to generate functionally diverse members. Here we identify numerous new SCD homologs in teleost fishes, using sequence data from EST and cDNA collections and genomic model species. Phylogenetic analyses of the deduced coding sequences produced only partially resolved molecular trees. The multiple SCD isoforms were, however, consistent with having arisen by an ancient gene duplication event in teleost fishes together with a more recent duplication in the tetraploid carp and possibly also salmonid lineages. Critical support for this interpretation comes from the comparison across all vertebrate groups of the gene order in the genomic environments of the SCD isoforms. Using syntenically-aligned chromosomal fragments from large-insert clones of common carp and grass carp together with those from genomically-sequenced model species we show that the ancient and modern SCD duplication events in the carp lineage were each associated with large chromosomal segment duplications, both possibly linked to whole genome duplications. By contrast, the 4 mouse isoforms likely arose by tandem duplications. Each duplication in the carp lineage gave rise to differentially expressed SCD isoforms, either induced by cold or diet as previously shown for the recent duplicated carp isoforms, or tissue-specific as demonstrated here for the ancient duplicate zebrafish isoforms.