BACKGROUND: Activated Akt expression (p-Akt) is reportedly increased in many melanomas as compared with benign nevi. The purpose of this study was to evaluate and compare p-Akt immunohistological staining in benign nevi, Spitz nevi and primary melanomas. METHODS: Immunostaining for phosphorylated Akt was performed in 41 melanocytic lesions previously classified as benign intradermal nevus (14 lesions), Spitz nevus (9 lesions) or melanoma (18 lesions). Lesions were graded for intensity of p-Akt staining by two independent observers (0, no staining; 1, slightly positive; 2, moderately positive; 3, highly positive). Scores were averaged, and statistical analyses were performed. RESULTS: Benign nevi showed less staining (mean score 1.18) compared with Spitz nevi (mean score 2.11) and melanomas (mean score 2.19). This difference was statistically significant between benign nevi and melanomas (p = 0.0047) and benign nevi and Spitz nevi (p = 0.0271). No statistical difference was detected in staining between Spitz nevi and melanomas (p = 0.8309). CONCLUSIONS: Activated Akt expression is increased in Spitz nevi and melanomas as compared with benign intradermal nevi, but is unlikely to prove useful in differentiating between the former.