Clinical and neuropathological data of a 50-year-old woman with an unusual multisystem degeneration are presented. Clinically the illness was characterized by progressive ataxia with ophthalmoplegia and multiple cranial nerve palsies. Neuropathological investigation showed a severe and selective degeneration of the dentato-rubral system, of the posterior columns and of several cranial nerve nuclei. The problems of differential diagnosis and classification are discussed.