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Background Repetitive traumatic brain injury (TBI) is associated with chronic traumatic encephalopathy (CTE), a progressive neurodegenerative disorder characterized by Alzheimer-like changes in the brain. CTE has been defined through neuropathological findings among deceased athletes and others exposed to repetitive TBI, but to date there are no definitive clinical criteria for CTE. Objective To evaluate the utility of currently proposed clinical criteria for CTE and suggest improvements. Methods We describe two well-characterized patients referred for evaluation of CTE and apply the four major proposed criteria for CTE. These criteria were further assessed in a cohort of patients referred to a neurobehavior clinic with or without a history of TBI. Results Without a CTE biomarker, the current criteria were of limited utility when applied to the two patient and the Neurobehavior cohort. Six items were extracted as potentially improving the clinical diagnosis of CTE: length of exposure to head impacts, a progressive course, specific psychiatric symptoms, frontal-executive dysfunction, parkinsonism and tremors, and targeted findings on neuroimaging. Conclusions The prevention and neurorehabilitation of CTE depends on clinical diagnosis, but, without a biomarker, the clinical diagnosis of CTE remains difficult. This report suggests that clinical criteria for CTE may be greatly improved with emphasis on several critical historical and clinical correlates of CTE.