Verruciform xanthoma is a rare variant of xanthoma that appears predominantly on oral mucosa and the anogenital area. The histologic features are characterized by marked accumulation of foam cells in the papillary dermis with verrucous epidermal acanthosis and hyperkeratosis. However, little is known of the nature or origin of foam cells. Recent studies have emphasized the crucial role of macrophage scavenger receptors in the formation of foam cells in atherogenesis. We examined the immunohistologic localization of scavenger receptors in genital verruciform xanthoma. We found that the massively infiltrated foam cells in the papillary dermis were CD68+ monocyte-macrophage lineage cells, and that the majority of CD68+ cells coexpressed scavenger receptors. The in situ staining pattern of scavenger receptor in foam cells was mainly of an intracytoplasmic vacuolar pattern similar to that of dermal resident macrophages found in normal skin. Furthermore, CD1a+ Langerhans cells, completely negative for scavenger receptor, were markedly decreased in number in verruciform xanthoma. These results indicate that scavenger receptor-bearing CD68+ cells are also actively involved in the development of cutaneous verruciform xanthoma, as has been shown to be the case in atherogenesis.