CJD is a lethal disease that is rapidly progressive with no cure. The disease can manifest with cognitive dysfunction, visual disturbance, insomnia, loss of dexterity/coordination, behavior or personality changes, mood disorders, unusual sensations and uncontrolled movements. With disease progression, the patient usually develops worsening dementia. The inconsistent clinical picture of sCJD makes diagnosis difficult. Atypical presentation is common and can delay diagnosis, symptomatic management and supportive treatment. Current diagnostic criteria include clinical suspicion, MRI (diffusion weighted imaging demonstrating cortical ribboning, long contagious segments of the basal ganglia and T2 reveals hyperintensity of the lenticular nuclei, without white matter enhancing lesions), EEG showing periodic sharp waves complexes, and CSF analysis with 14-3-3. Lumbar puncture is used to evaluate for varies rapidly progressive dementias. CSF cytology indicating 14-3-3 was previously applicable however it has yielded false positive results with a high sensitivity and low specificity. The 14-3-3 has been superseded and replaced by RT-QulC. The EUROPEAN (ZERR, updated 2017) criteria for sCJD diagnosis, includes RT-Qulc which allows ruling in CJD. Gold standard for diagnosis is a brain biopsy, however, it is invasive and carries a risk of brain damage and complications. Final diagnosis can ultimately be on autopsy. Traditional diagnostics have certain limitations, however the more specific the test, the greater the likelihood its accuracy will allow timely management. Unfortunately, there is no standard effective treatment for CJD. Therefore, precise diagnosis is imperative to allow comfort care, psychological support and symptomatic therapies. We hereby present a case of a 61 year old male who presented with probable seizure and altered mental status of unknown etiology. MRI findings were suggestive of bifrontal cortical ribboning that can be seen in seizure activity. CSF revealed positive 14-3-3 protein with a negative RT-Qulc. Although rapid deterioration raised concern for CJD, however, a prolonged hospitalization improved their mentation.