The genome of the cat flea, an ectoparasite of major veterinary importance and the first representative of the Siphonaptera, is highly unusual among arthropod genomes in showing a variable size and a very large number of gene duplications (Driscoll et al., 2020). The cat flea is the target of several classes of insecticides, justifying the description of its CYPome, the complement of P450s that are an important family of detoxification enzymes. 103 P450 genes were annotated on the nine chromosomes, with an additional 12 genes on small, extrachromosomal scaffolds. Only 34 genes were found as single sequences, with 47 duplicated two to four-fold. This included duplication of genes that are mostly single copy P450 genes in other arthropods. Large clusters of mitochondrial clan P450s were observed, resulting in a CYP12 bloom within this clan to 34 genes, a number of mitochondrial P450s not seen in other animals so far. The variable geometry of the cat flea CYPome poses a challenge to the study of P450 function in this species, and raises the question of the underlying causes of single copy control versus multicopy licence of P450 genes.