Degeneration of the white matter is uncommon is Creutzfeldt-Jakob disease (CJD), and when it occurs is usually mild, and limited in distribution. In the case of 77-year-old woman with CJD lasting 1 year, there was extensive degeneration of cerebral white matter in addition to severe loss of neurons and hypertrophic astrogliosis in cortex and striatum. The extent and severity of white matter lesions makes the case unusual.