In this review, changes that we have observed in the prevalence of mast cells in human sun-exposed skin, and their potential immunoregulatory role, are discussed. More specifically, in a study of Australian volunteers, the prevalence of dermal mast cells was increased in back-of-hand skin, anecdotally the most sun-exposed site of the body, but not in skin from buttock, inner arm or shoulder. By histological analysis of back-of-hand skin, there was a significant correlation between dermal mast cell prevalence and elastin content suggesting increased mast cell prevalence with photodamage. We hypothesised that these mast cells were immunomodulatory upon activation by sun exposure. However, no link was found between dermal mast cell prevalence in hand skin and the presence of basal cell carcinomas. Finally, we discuss other roles for increased numbers of mast cells in UV-exposed photodamaged skin.