Mycophenolate mofetil (MMF) has proved to be an efficacious and safe therapy in adult lupus nephritis. Recently, this drug has been suggested as a possible new alternative treatment also for juvenile-onset SLE (juvenile-SLE). A multicenter study has been performed to evaluate the efficacy and safety of MMF in controlling the disease activity in children and adolescents with juvenile-SLE. Our results show that MMF was effective in reducing the disease activity or as a steroid-sparing agent in 14 of 26 patients (54%), stabilised the disease in 8 (31%) and was ineffective in 4 (15%). In particular, in patients without renal involvement, a good response was registered in 9 of 13 patients (69%). Among those patients with renal involvement, MMF was effective in 5 of 13 patients (38%), partially effective in 4 (31%) and ineffective in 4 (31%). No severe side effects have been observed; only two patients stopped the drug because of severe diarrhoea and abdominal pain. With the limits of a retrospective study, MMF seems to be effective and safe for the treatment of juvenile-SLE, especially in patients with no renal involvement.