The etiology of verruciform xanthoma, a rare lesion that usually occurs in the oral mucosa, is unknown. A viral etiology has been speculated since extraoral lesions usually occur in the genitalia. We present, to the best of our knowledge, the first reported case of verruciform xanthoma in an immunocompromised patient with chronic graft versus host disease. Immunohistochemical studies showed a few Ham 56 (a macrophage marker) positive foam cells, both in the dermis and within the epidermis, supporting a role for an epidermal process in production of the foam cells. Staining for human papillomavirus protein (HPV) showed reactivity of some of the nuclei in the dermal histiocytes, but in situ hybridization for HPV types 6/11, 16/18, and 31, 33 was negative. These results support an epidermal process as the stimulus for the foam cell formation but fail to demonstrate HPV as the cause.