Neurological complications may occur in the course of Waldenström's macroglobulinemia (Wm). These complications affect both the central and peripheral nervous system. Pathogenesis is debated and several mechanisms have been suggested. Direct malignant lymphoid infiltration (MLI) is very rare and has only been reported in a few cases. Case report. A 67-year-old woman suffered from Wm for 10 years before she presented neurological complications of the disease. She did not receive any specific treatment for Wm owing to a lack of symptoms. The neurological complications consisted of peripheral demyelinating polyneuropathy and MLI of the nervous system. This infiltration was located in the lower perimedullary and cauda equina roots regions, with possible centromedullary involvement. Indirect demonstration of MLI was achieved through non-invasive tests including magnetic resonance imaging and detailed cerebrospinal fluid examination. General and intrathecal chemotherapy led to clinical, biological and radiological improvement over a four-year period.