Background Nevus depigmentosus (ND) is known to be a rare congenital, nonprogressive disorder characterized by a hypopigmented lesion that remains stable over time. There have been only few studies of clinical and histopathologic characteristics of ND, and the etiopathogenesis is not fully established. Objective The purpose of this study was to investigate the clinical and histopathologic characteristics of ND. Methods A clinical survey was carried out with 60 patients given the diagnosis of ND. Punch biopsies (2 mm) from lesional and perilesional normal skin were performed. The sections were stained with hematoxylin-eosin, Fontana-Masson, antibodies to S-100 protein, MART-1, NKI/beteb, CD1a, CD3, CD20, and CD68. Results The lesions were usually present before the age of 3 years (68.3%), but some lesions appeared later in childhood (31.7%). In all, 27 patients (45%) had one lesion, but there were 14 patients (23.3%) who had more than 10 lesions. Fontana-Masson stain showed that the amount of melanin was significantly decreased in ND skin compared with perilesional normal skin. Melanocyte counts were significantly decreased in ND skin when stained with antibodies to GP-100 and MART-1. However, there were no significant differences in the number of melanocytes identified as S-100 protein–positive cells. There were no significant differences in histologic findings or dermal inflammatory infiltrates between ND skin and perilesional normal skin. Limitations Only 29 patients (48.3%) were followed up, and the average follow-up period after initial diagnosis was relatively short (68 months); therefore, these overall results may not be representative of the clinical course of the patients. Conclusion Only 18 patients (30.0%) presented with ND since birth and only 27 patients (45.0%) had one lesion. Both the amount of melanin and the number of melanocytes in ND skin were decreased in patients with ND. Therefore, both clinical and histologic findings should be considered together to make a diagnosis of ND.