Sphingomyelin (SM) is a membrane phospholipid that is widely distributed in Metazoa; it is the major constituent of myelin sheaths in vertebrates. In mammals, two genes (SMS1 and SMS2) are responsible for its synthesis. No SM-producing genes have been clearly identified in insects and crustaceans (Ecdysozoa) despite the presence of a myelin sheath-like structure in shrimps. Since the rapid transmission of electrical signals requires the use of an insulating material in the nerve, it is possible that the convergent evolution of enzymes to synthesize the insulating compounds for the nervous system also occurred in animals other than vertebrates. Our exhaustive phylogenetic search for metazoan SM synthase identified an Ecdysozoa-specific SM synthase candidate, SMSe, which is absent in Drosophila and Lophotrochozoa. All Ecdysozoa lack the homolog of myelin basic- and proteolipid proteins present in mammals. We propose an evolutionary path of SM synthase and discuss the origin of the myelin structure in Metazoa.