There has been persistent uncertainty as to whether lesions of the cerebellum are associated with clinically significant disturbances of behavior and cognition. To address this question, 20 patients with diseases confined to the cerebellum were studied prospectively over a 7-year period and the nature and severity of the changes in neurological and mental function were evaluated. Neurological examination, bedside mental state testing, neuropsychological studies, and anatomic neuroimaging were administered at the time of presentation and during follow-up assessments. Behavioral changes were clinically prominent in patients with lesions involving the posterior lobe of the cerebellum and the vermis and, in some cases, overwhelmed other aspects of the presentation. These changes were characterized by an impairment of working memory, planning, set shifting, verbal fluency, abstract reasoning, and perseveration; visual-spatial disorganization, visual memory deficits, and logical sequencing; and a bland or frankly inappropriate affect. Lesions of the anterior lobe of the cerebellum produced only minor changes in executive and visual-spatial functions. This newly defined clinical entity is called the cerebellar cognitive affective syndrome. The constellation of deficits is suggestive of disruption of the cerebellar modulation of neural circuits than link frontal, parietal, temporal, and limbic cortices with the cerebellum.