Waldenström macroglobulinaemia is a low-grade, lymphoplasmacytic lymphoma that is responsive to rituximab. We report the role of a minor response in predicting overall outcomes. We extended follow-up of a previously described cohort (n = 69) treated with 4 weekly doses of rituximab and observed durable responses (median time to progression, 30 months; 5-year survival rate, 66%). Patients achieving a minor response [25-50% immunoglobulin M (IgM) reduction] appeared to do as well as those achieving an objective response (>50% IgM reduction), which suggests that more aggressive or intensive therapy for minor responders is not required. Future studies of Waldenström macroglobulinaemia should report minor responses because they are associated with clinically meaningful benefits. This trial was registered at http://www.clinicaltrials.gov as #NCT00005609.