Rituximab is a chimeric anti-CD20 monoclonal antibody that has approval for single agent therapy in the treatment of relapsed/refractory low grade or follicular non-Hodgkin's Lymphoma. In published phase II trials, molecular remissions of PCR detectable t(14;18) disease in the peripheral blood have been reported in up to 62% of patients by three months. We report a case of a patient who achieved prolonged clinical and molecular remission following a single four week course of Rituximab that has exceeded any previous remission achieved with chemo-radiotherapy. The implications of molecular remission as a surrogate of clinical remission and molecular relapse as a harbinger of clinical relapse are reviewed and discussed.