Patients treated with immunosuppressive agents are prone to developing lymphoproliferative disorders, in particular Epstein-Barr virus–associated lymphoproliferative disease. This complication was reported first in post-transplanted patients treated with cyclosporine, and, more recently, in patients receiving long-term methotrexate therapy for inflammatory disease. We describe the case of a 70-year-old female patient with multifocal cutaneous lymphoproliferative disease occurring in the course of long-term, weekly methotrexate therapy for rheumatoid arthritis. Immunohistochemical study revealed the presence of latent membrane protein within neoplastic cells. Cutaneous lesions initially continued to increase in number and size in the first 2 months and finally disappeared completely within 5 months after discontinuation of methotrexate. The patient is now in complete remission with 12-months’ follow-up. Despite initial progression after cessation of immunosuppressive therapy, Epstein-Barr virus–induced lymphoproliferative disease may disappear completely within months, thus avoiding pointless chemotherapy.