Nephrotic syndrome secondary to minimal change disease (MCNS) usually is considered to have a good renal prognosis, but frequency of relapses and steroid dependency are therapeutic challenges to physicians. Treatment of patients with multiple relapses remains controversial because few control studies are available. We report the case of a 23-year-old woman of Malian origin who experienced more than 30 relapses of MCNS. Long-term remission was observed only with rituximab (anti-CD20 antibody) treatment after step-by-step use of all currently available medications for MCNS were unsuccessful. Our observation is the first report of efficacy of rituximab during multirelapsing MCNS in an adult patient with a significant follow-up and no adjuvant therapy. This case suggests a role of B cells in MCNS, possibly by regulating T-cell function.