A 91-year-old woman who had been taking methotrexate for approximately 5 years for rheumatoid arthritis developed papules and nodules on her face that enlarged during 6 months. A series of biopsy specimens demonstrated a lymphoplasmacytic infiltrate with increasingly atypical histopathologic features that resembled diffuse large B-cell lymphoma. Epstein-Barr virus was not identified. Withdrawal of methotrexate resulted in complete resolution of all lesions within 8 weeks. This case illustrates the rare occurrence of methotrexate-associated lymphoproliferative disorder with primary presentation in the skin and documents clinical and histopathologic progression from early changes to fully developed lesions.