A case is reported in which a patient with a rheumatoid factor-negative rheumatoid arthritis developed rheumatoid nodules in the penis during treatment with methotrexate. The development of rheumatoid nodules in seronegative rheumatoid arthritis patients is extremely rare. An acceleration of rheumatoid nodules in methotrexate-treated reheumatoid arthritis patients is reported in literature. Regarding the case reported here, we propose a causal relationship between methotrexate-treatment and the development of rheumatoid nodules in our patient. Methotrexate should not be the preferential treatment for patients with rheumatoid arthritis developing rheumatoid nodules and suffering from vasculitis.