Background: Chemical communication is an important aspect of the behavioural ecology of a wide range of mammals. In dogs and other carnivores, anal sac glands are thought to convey information to conspecifics by secreting a pallet of small volatile molecules produced by symbiotic bacteria. Because these glands are unique to carnivores, it is unclear how their secretions relate to those of other placental mammals that make use of different tissues and secretions for chemical communication. Here we analyse the anal sac glands of domestic dogs to verify the secretion of proteins and infer their evolutionary relationship to those involved in the chemical communication of non-carnivoran mammals. Results: Proteomic analysis of anal sac gland secretions of 17 dogs revealed the consistently abundant presence of three related proteins. Homology searches against online databases indicate that these proteins are evolutionary related to ‘odorant binding proteins’ (OBPs) found in a wide range of mammalian secretions and known to contribute to chemical communication. Screening of the dog’s genome sequence show that the newly discovered OBPs are encoded by a single cluster of three genes in the pseudoautosomal region of the X-chromosome. Comparative genomic screening indicates that the same locus is shared by a wide range of placental mammals and that it originated at least before the radiation of extant placental orders. Phylogenetic analyses suggest a dynamic evolution of gene duplication and loss, resulting in large gene clusters in some placental taxa and recurrent loss of this locus in others. The homology of OBPs in canid anal sac glands and those found in other mammalian secretions implies that these proteins maintained a function in chemical communication throughout mammalian evolutionary history by multiple shifts in expression between secretory tissues involved in signal release and nasal mucosa involved in signal reception. Conclusions: Our study elucidates a poorly understood part of the biology of a species that lives in close association with humans. In addition, it shows that the protein repertoire underlying chemical communication in mammals is more evolutionarily stable than the variation of involved glands and tissues would suggest.