Creutzfeldt-Jakob disease (CJD) is a rapidly progressive prion disease that causes deficits involveing movement, cognition, and mental status. The clinical heterogeneity of the disease can make diagnosis difficult. Thorough neurologic, cognitive, and psychiatric examinations are necessary for observing its clinical features. In this case report we describe a 62-year-old male patient who was initially followed with a diagnosis of depression and later was diagnosed with CJD, The patient had a one-year history of anhedonia, loss of interest, social withdrawal, anxiety and decrease in speech and was given paroxetin 20 mg/day with a diagnosis of depression. During follow up, neurological symptoms including ataxia and rigidity became evident and dementia and akinetic mutism developed in a rapidly progressive course. Although electroencephalography (EEG) and magnetic resonance imaging (MRI) revealed nonspecific findings initially, typical findings for CJD were seen during the follow up. The positive 14-3-3 protein in CSF supported the diagnosis. The aim of this report is to emphasize the fact that CJD may present with different psychiatric symptoms and can be initially misdiagnosed. CJD should be considered in the differential diagnosis of patients who have focal neurological signs in addition to psychiatric symptoms. Repeated neurological examinations, EEG and cranial MRI may help in the diagnosis of these patients.