BACKGROUND: Verruciform xanthoma is an uncommon lesion that occurs primarily on the mucous membranes and more rarely on the skin. A few authors have reported the extremely rare occurrence of multiple lesions. Triggering or enhancing factors have been occasionally described such as an underlying immunosuppression or associated inflammatory mucous or skin diseases. We report, to the best of our knowledge, the first case report of multiple verruciform xanthomas of the oral mucosa in a patient with graft-versus-host disease with specific oral lesions. CASE REPORT: A 57 year-old man presented with an 8-year history of chronic myeloid leukemia. He was considered in complete remission for leukemia after allogenic bone marrow transplantation. Nevertheless, he was still treated with immunosuppressive drugs for oral and cutaneous lesions of chronic graft-versus-host disease. In this context, the patient presented two symmetric lesions of the gingiva. These lesions had progressed over several months. The clinical presentation was similar, with a yellowish and verrucous aspect and a sessile base. Histologic and immunohistochemical analysis led to the diagnosis of multiple verruciform xanthomas. DISCUSSION: The occurrence of multiple lesions of this rare tumour in our patient was probably not fortuitous. Immunosuppression associated with oral chronic inflammatory lesions are certainly involved in the pathogenesis of these two verruciform xanthomas, for example following degeneration of epithelial cells after local chronic irritation and/or reduction of Langerhans cells. Systematic research of enhancing or triggering factors seems essential in verruciform xanthoma.