Rituximab, a monoclonal antibody against B-cell membrane marker CD-20, is an effective treatment for immunoglobulin M (IgM) monoclonal anti-myelin-associated glycoprotein (MAG) neuropathies. We report a patient with an autonomic and painful sensory neuropathy associated with an IgM lambda monoclonal gammopathy, responsive to rituximab. Treatment resulted in a decline in total IgM and improvement in the patient's painful neuropathy and dysautonomia. Rituximab may be an effective and tolerable treatment for autonomic and sensory neuropathy associated with IgM monoclonal gammopathy.