Neoplastic melanocytes may exhibit certain differentiation characteristics of other neural-crest derivatives. We aimed to study the expression of microtubule-associated protein 2 (MAP-2) in different types of melanocytic skin lesions. Paraffin-embedded sections of 42 benign nevi (BN), 22 dysplastic nevi (DN), 45 superficial spreading melanomas (SSMs), and 15 subcutaneous melanoma metastases were immunohistologically assessed using the monoclonal mouse MAP-2ab antibody (Zytomed, Berlin, Germany). The percentage MAP-2 expression of DN and SSMs was significantly increased compared with BN. Moreover, subcutaneous melanoma metastases showed significantly decreased MAP-2 expression compared with DN and SSMs. In SSMs, MAP-2 expression significantly correlated with the Breslow vertical tumor thickness, Clark level, and stage of disease. We observed that MAP-2 is differentially expressed during the development and progression of benign and malignant melanocytic skin lesions. In contrast with the findings of previous studies, our data indicate that MAP-2 is a moderately positive predictor of the progression of SSMs.