Background: Many case studies of lichen sclerosus et atrophicus (LSA) have reported an association of vitiligo. LSA may result in oral and genital vitiligoid depigmentation without textural changes and needs to be differentiated from vitiligo. Objectives: To investigate and compare pigmentary characteristics of LSA and vitiligo lesions by using histochemical and immunohistochemical staining Methods: Twenty-seven and forty-six patients diagnosed with LSA and vitiligo respectively, from March 2009 to December 2018 at Ajou University Hospital were included. Their medical charts and skin biopsy specimens were retrospectively reviewed. Additionally, Fontana-Masson staining for melanin and immunohistochemical staining for Melan-A, NKI/beteb, tyrosinase, and microphthalmiaassociated transcription factor were performed. Results: Melanin pigment was significantly increased in the epidermis of LSA compared to that of vitiligo in patients. The number of melanocytes and their activity were also significantly increased in LSA samples. Even though there are statistical differences, 48.1% of LSA patients showed both of fewer melanin pigmentation and number of melanocytes than that of average amount of vitiligo. Conclusion: In our study, melanin pigmentation and number of melanocyte in many cases of LSA was greatly decreased like vitiligo. Therefore, to differentiate the vitiligo and LSA, both clinical and histological findings must be reviewed comprehensively.