A 71-year-old-woman was admitted to the S. Eugenio Hospital for a history of progressively impaired standing and gait. Anamnesis revealed systemic hypertension, gastric polyposis and juvenile pulmonary tuberculosis. Neurological examination showed a severe truncal and gait ataxia, without any sensory-motor impairment. Motor and somato-sensory evoked potentials were normal. Brain Magnetic Resonance Imaging (MRI) showed minimal signs of chronic ischemia only at a supratentorial level. Cerebral Single Photon Emission Computed Tomography, spinal MRI, total body computed tomography, Esophagogastroduodenoscopy, and finally total body Positron Emission Tomography resulted negative for neoplasms. Oncological serum markers were negative. Serum antibody against Purkinje's cells (Anti-Yo) was detected and titer was 1:80, while normally it should be undetectable. Other autoantibodies (Anti-Hu, Anti-Ri) were undetectable. Two sessions of plasma exchange (PE) were thus performed, leading to a rapid, marked and durable improvement of standing and gait and to a reduction of the autoantibody, which became undetectable. No serious adverse effect was noted. Although no definite therapy for autoimmune cerebellar ataxia has been established, PE should be considered as one of the main therapeutic choices.