Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating neurological disorder caused by JC virus. Immunocompromised patients such as those with chronic lymphocytic leukemia, AIDS and following organ transplantation are at increased risk. We report a patient with PML complicating longstanding Waldenström's macroglobulinaemia. Although PML is a rare occurrence, the newer highly immunosuppressive treatment approaches for patients with lymphoproliferative disorders necessitate a high index of clinical suspicion. The diagnosis should be considered in patients with compatible clinical features who have received long-term immunosuppressive treatments recognized to impair cellular immunity.