The risk of skin cancers such as basal cell carcinoma and squamous cell carcinoma varies greatly across the body, and it is known that healthy aged skin cells often harbor cancer driver mutations, but whether these observations are connected has not been determined. Fowler and colleagues discovered that the mutation density in healthy human skin differed from location to location across the body. Common sites for skin cancer, such as the forearm, bore more mutations than uncommon sites, and the mutation profile suggested UV radiation as a cause. Interestingly, not only was there selection for cancer-associated mutations in healthy skin, but the DNA repair mechanisms used varied based on site. For more information, see the article by Fowler and colleagues on page 340.