Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative condition with a 
rapid disease course and a mortality rate of 100%. Several forms of the disease 
have been described, and the most common is the sporadic type. The most 
challenging aspect of this disease is its diagnosis-the gold standard for 
definitive diagnosis is considered to be histopathological confirmation-but 
newer tests are providing means for an antemortem diagnosis in ways less 
invasive than brain biopsy. Imaging studies, electroencephalography, and 
biomarkers are used in conjunction with the clinical picture to try to make the 
diagnosis of CJD without brain tissue samples, and all of these are reviewed in 
this article. The current diagnostic criteria are limited; test sensitivity and 
specificity varies with the genetics of the disease as well as the clinical 
stage. Physicians may be unsure of all diagnostic testing available, and may 
order outdated tests or prematurely request a brain biopsy when the diagnostic 
workup is incomplete. The authors review CJD, discuss the role of brain biopsy 
in this patient population, provide a diagnostic pathway for the patient 
presenting with rapidly progressive dementia, and propose newer diagnostic 
criteria.