The subset of nevi occurring at special sites (eg, acral skin, anogeni-tal region, breast, ear, flexural surfaces) have normal histologic variations that preclude the use of routinely used diagnostic criteria for malignancy. Suggested criteria for differentiating malignant special-site lesions from benign lesions have been described, but there is an unmet need for a validated test aiding in the delineation of benign and malignant lesions at special sites. Preferentially expressed antigen of melanoma (PRAME) expression has been characterized as a relatively specific marker of melanoma, but not within the specific population of special-site lesions. This study aimed to determine if PRAME may serve as a specific marker of melanoma within the population of special-sites lesions.