Neuroborreliosis has very low prevalence in Kentucky and coma due to Lyme disease is uncommon in North America. A patient diagnosed with Lyme disease in Kentucky, based on coma, typical inflammatory changes on brain imaging, and a positive ELISA resulted in an erroneous clinical impression. Diagnosis should have been confirmed by a positive result on Western Blot, polymerase chain reaction (PCR), or real-time polymerase chain reaction (RT-PCR) testing. Physicians must apply careful consideration before diagnosing a rare disease in areas where that condition is uncommon without first eliminating other differential options. Neuroborreliosis clinicalfindings are nonspecific and often require confirmatory testing, especially in nonclassical case presentations.