Background: Langerhans cells are important in the pathogenesis of leprosy. A recent study reported that these cells were almost absent in the epidermis overlying lepromatous lesions. Objective: To investigate a possible relationship between the number of Langerhans cells and the histopathologic spectrum of lesions in patients with leprosy. Methods: An immunohistochemical staining for S100 protein was used to study skin punch biopsies of patients with leprosy and to quantify S100-positive Langerhans cells in the epidermis. Results: A progressively significant reduction in the number of Langerhans cells was found from tuberculoid to lepromatous skin lesions. Langerhans cells were significantly less frequent in lepromatous and borderline lepromatous as compared to either tuberculoid or borderline tuberculoid leprosy. Conclusion: In view of the fact that adequate numbers of dendritic cells are recruited to the dermis, their maturation/migration to Langerhans cells in the epidermis is impaired in lepromatous leprosy.