Cold agglutinin disease (CAD) is a rare cause of anaemia in patients with systemic lupus erythematosus (SLE). CAD is usually refractory to glucocorticosteroid, and other immunosuppressive and/or cytotoxic therapies. We report the case of a 55-years old woman with SLE and CAD that did not respond to high-dose methylprednisolone, cyclosporin A, and double filtration plasma pheresis. Because several recent case reports and studies have indicated promising results of rituximab treatment for CAD and for SLE, rituximab was given weekly at 375 mg/m(2) in two doses. The rituximab was well tolerated, and there were no adverse effects. The hemolysis and SLE improved markedly, and the patient remained disease free eight months later. This is the first report of successful rituximab treatment of CAD in a patient with SLE. We conclude that rituximab is worth trying in such patients if they fail to respond to conventional treatment.