A 69-year-old woman was treated with immunosuppressive agents (methotrexate, tacrolimus, cyclosporine, etanercept, adalimumab, azathioprine, and mycophenolate mofetil) for a 30-year history of systemic lupus erythematosus, rheumatoid arthritis, and interstitial pneumonia. She presented to our hospital for evaluation of right-sided hemiparesis. Magnetic resonance imaging revealed a ring-enhanced mass lesion (maximum diameter 36mm) in the left parietal lobe. She was hospitalized for further evaluation and treatment of suspected high-grade glioma, metastatic brain tumor, and malignant lymphoma. We performed subtotal tumor resection, and histopathological evaluation of the resected specimen confirmed diagnosis of diffuse large-cell B-cell lymphoma, an iatrogenic lymphoproliferative disease caused by immunosuppressive drugs. This disorder was attributed to mycophenolate mofetil therapy initiated 1 year before symptom onset. Mycophenolate mofetil therapy was discontinued, and the patient received six cycles of rituximab and local radiation. Iatrogenic lymphoproliferative disease is known to occur during mycophenolate mofetil treatment ; however, primary lymphoproliferative disease of the central nervous system associated with mycophenolate mofetil therapy is rare.