The new analysis of the expression of cell cycle regulators (used in various neoplasms) and the nominal immunohistologic assays still represent valid and feasible diagnostic methods in most pathology practice. We examined 114 paraffin-embedded histologic specimens of melanocytic cutaneous lesions. The primary objective of this study was to explore diagnostic potential of the two important cell cycle regulators, p16 and Ki67, also evaluating the variations of expression by use of a semi quantitative graded scale. Another aim was to study the hypothetical correlation between p16 expression (in melanocytic and non-melanocytic lesions) and two independent variables, i.e. patient age and anatomical sites (sun exposed or non-sun exposed) of the lesions. Cell population was considered positive for antibody-specific p16 and Ki67 when at least 33% of the cells showed well-defined nuclear and/or cytoplasmic staining. A special p16 and Ki67 trend was found only in Spitz nevus, atypical Spitz nevus and invasive malignant melanoma (MM). No discriminative values were found regarding other lesions (junctional melanocytic nevus, MM in situ, superficially spreading MM, non-melanoma skin cancers). p16 was over-expressed on sun exposed sites and hypo-expressed on non-sun exposed areas, yielding a statistically significant correlation (p<0.03). According to patient age, p16 was over-expressed in patients aged ≥61 and hypo-expressed in patients aged ≤60 (p=0.09).