Background: Nevus depigmentosus is defined as a congenital nonprogressive hypopigmented macule or patch that is stable in its relative size and distribution throughout life. The pathogenesis and histopathologic characteristics of nevus depigmentosus is not yet fully established. Objective: The purpose of this study was to investigate the clinical and histopathologic characteristics of nevus depigmentosus as well as its pathogenesis. Methods: A clinical survey was done with 67 patients diagnosed as having nevus depigmentosus. Two skin biopsy specimens each were taken from 18 patients: one from the central part of the depigmented lesion and another from the border of the lesion, including peri-lesional normal skin. The sections were stained with hematoxylin-eosin, Fontana-Masson, and S-100 protein. Ultrastructural evaluation was also done to detect changes of the melanocytes. Results: The lesions were mostly present before 3 years of age (92.5%), but some lesions also appeared later in childhood (7.5%). The back and buttocks were the most commonly affected sites, followed by the chest and the abdomen, the face, the neck, and the arms. Forty patients (59.7%) had the isolated type of nevus depigmentosus and 27 patients (40.3%) had the segmental type. Histopathologic studies showed that the staining ability of Fontana-Masson in nevus depigmentosus lesions decreased compared with perilesional normal skin. However, there were no changes in the numbers of melanocytes identified as S-100-positive cells in the basal layer. Electronmicroscopic studies revealed a great reduction in the number of melanosomes in melanocytes and some membrane-bound aggregated melanosomes were observed in keratinocytes. Conclusion: The results of this study support the hypothesis that nevus depigmentosus is caused by the functional defects of melanocytes and the morphologic abnormalities of melanosomes.(J Am Acad Dermatol 1999;40:21-6.)