We report a case of dermatomyositis associated with rheumatoid arthritis, Hashimoto thyroiditis, and diabetes mellitus responsive only to combination of rituximab with mycophenolate. A 42-year-old woman presented with proximal muscle weakness, myalgias, fever, night sweats, and shortness of breath. Creatinine kinase was 8155 IU/L, and muscle biopsy was diagnostic of dermatomyositis. She was started on glucocorticoids; her systemic symptoms improved, but her muscle weakness persisted. She was serially treated with intravenous immunoglobulin, azathioprine, and mycophenolate mofetil without improvement in her weakness. She responded dramatically to combination therapy with rituximab and mycophenolate, with improvement in strength and normalization of creatinine kinase. She has been well controlled on rituximab infusion every 6 months and maintenance mycophenolate mofetil.