Spitz nevi on acral sites are rare and poorly documented. The combination of Spitzoid cytomorphology and atypical architectural features of the junctional component may lead to an erroneous diagnosis of melanoma. To study the clinicopthologic and immunohistochemical features, 50 Spitz nevi localized on the distal extremities were retrieved from departmental files. Clinical data and follow-up were obtained and the histologic features were analyzed. P16 and P21 immunohistochemical staining of the dermal component was compared with that of 10 acral lentiginous melanomas and 10 acral nevi. Acral Spitz nevi affected young adults (median: 24.5 y; range: 4 to 61 y) with a female predominence and a predilection for the feet. They were pigmented measuring 1 to 15 mm (median: 4 mm). Follow-up, available for 45 patients (median: 48 mo; range: 4 to 228 mo), revealed no local recurrence, metastasis or mortality. Histologically, acral Spitz nevi were composed of large epithelioid and/or spindled melanocytes. They were well circumscribed with occasional asymmetry. The junctional component was broad with a lentiginous and nested growth and shoulder formation. Marked pagetoid spread and transepidermal elimination of junctional nests were common features. Focal active regression of the dermal component was frequently noted but there was no nuclear pleomorphism or dermal mitotic activity. Acral Spitz nevi were characterized by strong and diffuse P16 and P21 expression, which differs from acral nevi and acral lentiginous melanoma. Acral Spitz nevi are a distinctive subgroup of Spitz nevi with benign behavior. Awareness of the subtle histologic differentiating features and the distinctive P16/P21 expression pattern allows separation from melanoma.