A case of Creutzfeldt-Jakob disease (CJD) with presenting Wernicke encephalopathy (WE)-like symptoms and severe insomnia is presented. An 80-year-old alcoholic man with a 6 month history of tremors, ataxia, memory loss and confabulation, developed profound insomnia, confusion, and delirium with vivid hallucinations. Polysomnography revealed a marked reduction of sleep time, with central-type sleep apnea. Neither myoclonus nor periodic synchronous discharge (PSD) was observed. An autopsy revealed diffuse spongiform changes and astrocytosis throughout the cerebral gray matter, with severe involvement of the mammillary bodies and thalamus. Prion protein (PrP) immunostaining was positive in kuru plaques in the cerebellum, PrP polymorphism at codon 129 was heterozygous Met/Val, and proteinase K resistant PrP (PrP(res)) was demonstrated by Western blotting. The lack of necrotizing lesions in the mammillary bodies, thalamus, and periaqueductal gray matter could rule out WE. The data suggest that the present case of CJD is consistent with PrP(res) type 2 (CJD M/V 2), but was unique in the lack of some typical CJD signs and the presence of signs of WE and sleep abnormalities.