Accurate classification of spitzoid melanocytic neoplasms, including Spitz nevi, atypical Spitz nevi, and spitzoid melanomas, poses a challenge to dermatologists and pathologist due to the overlap of their clinical, dermatoscopic and pathohistological features. Immunohistochemistry has been used as a safe but not completely specific way to diagnose this type of neoplasms as a supplement to the pathohistological analysis. To this date, immunohistochemical expression of p16 (CDKN2A) , Ki-67 and HMB-45 gradient have been in the evaluation of spitzoid lesions. However, p16 proved to be an unreliable marker in the interpretation of borderline and malignant spitzoid lesions since the loss of its expression can be seen in many benign lesions, and is not necessary present in melanoma. Unlike p16, p15, which is a tumor suppressor encoded by CDKN2B, seems to be a very specific marker because loss of its expression is much more common in melanoma than in Spitz nevi. This indicates that p15 loss may be a better marker of malignancy and also suggests that p15 could be a superior and more commonly used immunohistochemical marker than p16 in the evaluation of spitzoid melanocytic neoplasms in the future.