AbstractThe structure of the skin may evolve rapidly during a biological invasion, for two reasons. First, novel abiotic challenges such as hydric conditions may modify selection of traits (such as skin thickness) that determine rates of evaporative water loss. Second, invaders might benefit from enhanced rates of dispersal, with locomotion possibly facilitated by thinner (and hence more flexible) skin. We quantified thickness of layers of the skin in cane toads (Rhinella marina) from the native range (Brazil), a stepping-stone population (Hawaii), and the invaded range in Australia. Overall, the skin is thinner in cane toads in Australia than in the native range, consistent with selection on mobility. However, layers that regulate water exchange (epidermal stratum corneum and dermal ground substance layer) are thicker in Australia, retarding water loss in hot dry conditions. Within Australia, epidermal thickness increased as the toads colonized more arid regions, but then decreased in the arid Kimberley region. That curvilinearity might reflect spatial sorting, whereby mobile (thin-skinned) individuals dominate the invasion front; or the toads’ restriction to moist sites in this arid landscape may reduce the importance of water-conservation. Further work is needed to clarify the roles of adaptation versus phenotypic plasticity in generating the strong geographic variation in skin structure among populations of cane toads.