OBJECTIVE: Some melanocytic lesions can be difficult to diagnose because of ambiguous histological and immunohistochemical features. Morphometric features of melanocytes in the upper and lower parts of a challenging lesion may help to facilitate an accurate diagnosis. STUDY DESIGN: We studied 32 cases of invasive cutaneous melanoma, 35 cases of mild or moderate dysplastic nevus, and 31 cases of benign melanocytic nevus. All cases were immunostained with Sox10. The nuclear areas of 30 melanocytes were measured on each papillary (upper [U]) dermis and reticular dermis/subcutaneous tissue (lower [L]) in all cases by using the Image J analysis program. Then, a maturation index (U/L) was calculated for each case. Also, cutaneous melanomas were categorized into 2 groups that displayed pseudomaturation or the lack of it. RESULTS: Mean maturation index was 1.04±0.29 in melanomas, 1.23±0.28 in dysplastic nevi, and 1.52±0.33 in benign melanocytic nevi, respectively. There were statistically significant differences between melanoma and dysplastic nevus (p=0.012) and between melanoma and benign melanocytic nevus (p<0.001) for the maturation index. Although pseudomaturation was associated with low mitotic activity and thin Breslow thickness, there was no significant difference between survival distributions of 2 melanoma groups. CONCLUSION: Calculation of the maturation index can be used as a supporting tool for the differential diagnosis of challenging cases. However, it may possess limitation for evaluation of nevoid melanoma, melanoma in situ, or clonal nevus. © Science Printers and Publishers, Inc.