Abstract

Distinctive mammalian traits, such as endothermy (warm- bloodedness), a muscular diaphragm, large brain size, fur, and a highly specialized dentition, including diphyodonty, prismatic enamel, and a functionally regionalized tooth row (heterodonty), are the product of more than 300 million years of evolutionary divergence from reptiles and other tetrapods. The sequence and timing of these adaptations are captured in the fossil record of premammalian synapsids, but an understanding of the evolutionary context of mammalian disease, including cancer, remains elusive. We report the first instance, to our knowledge, of a tumor in a 255-million-year- old mammalian forebear and comment on the implications for establishing the phylogenetic and physiological conditions under which such pathologic features first arose.