Infectious prion proteins - the causative agents of the fatal neurodegenerative disorder Creutzfeldt-Jakob disease - can be detected in the skin of afflicted individuals, researchers now report. The findings raise the remote possibility that prion diseases may be transmitted through surgical procedures involving the skin. Prion disorders like Creutzfeldt-Jakob disease arise when misfolded versions of a central nervous system-dwelling protein convert its normal counterparts into harmful conformations. Although Creutzfeldt-Jakob disease was known to be transmissible through corneal transplants and contaminated surgical tools that contacted brain or nervous system tissue, scientists have found scant evidence for misfolded prions residing in other regions of the body. Here, Christina Orru and colleagues used a highly sensitive detection method called RT-QulC to search for infectious prions in skin samples from 23 Creutzfeldt-Jakob disease patients, as well as 15 individuals with unrelated neurological disorders. They found infectious prions in at least one skin sample from all Creutzfeldt-Jakob disease patients tested, most commonly in biopsies taken from the area near the ear, whereas none of the people without Creutzfeldt-Jakob disease tested positive. Notably, prion amounts detected in skin samples were roughly 1,000 to 100,000 less than found in brain tissue, and a less sensitive detection method only detected prions in skin samples from five Creutzfeldt-Jakob disease patients. Inoculations of skin from two Creutzfeldt-Jakob disease patients also lead to prion disease in two different mouse models. The authors emphasize that prion diseases cannot be spread through casual contact, and call for further studies to uncover how the misfolded proteins come to reside in the skin.