Copper membrane monooxygenases (CuMMOs) oxidize ammonia, methane and some short-chain alkanes and alkenes. They are encoded by three genes, usually in an operon of . We aligned operons from 66 microbial genomes, including members of the -, -, and and the candidate phylum NC10. Phylogenetic and compositional analyses were used to reconstruct the evolutionary history of the enzyme and detect potential lateral gene transfer (LGT) events. The phylogenetic analyses showed at least 10 clusters corresponding to a combination of substrate specificity and bacterial taxonomy, but with no overriding structure based on either function or taxonomy alone. Adaptation of the enzyme to preferentially oxidize either ammonia or methane has occurred more than once. Individual phylogenies of all three genes, and , closely matched, indicating that this operon evolved or was consistently transferred as a unit, with the possible exception of the methane monooxygenase operons in , where the gene has a distinct phylogeny from and . Compositional analyses indicated that some clusters of operons (for example, the in gammaproteobacterial methanotrophs and the in betaproteobacterial nitrifiers) were compositionally very different from their genomes, possibly indicating recent lateral transfer of these operons. The combined phylogenetic and compositional analyses support the hypothesis that an ancestor of the nitrifying bacterium was the donor of methane monooxygenase (pMMO) to both the alphaproteobacterial and gammaproteobacterial methanotrophs, but that before this event the gammaproteobacterial methanotrophs originally possessed another CuMMO (Pxm), which has since been lost in many species.