This report documents a case of a patient who developed neuropathy, which presented as dental pain and was later diagnosed with Lyme disease. A healthy female patient presented to the endodontist with toothache symptoms. Her symptoms included intense pain in the left mandible irradiating into the temporalis area and through her neck, tingling on the lower left lip and left side of her tongue. She also reported feeling of sweats and chills the night before, as well as an altered sensation in her shoulder and arm. The pain was not alleviated by over-the-counter analgesics. Both Intra-oral and radiographic examinations did not reveal any abnormalities and the patient was presented with the following differential diagnoses: 1) cardiac issues; 2) trigeminal neuralgia; 3) temporomandibular dysfunction. She presented to the emergency room at the local hospital for assessment on the same day. After having had some tests performed both a stroke and myocardial infarction were ruled out. The following morning, she noticed a bump in the posterior area of her left upper thigh where an erythema with a bull’s eye appearance was observed. She presented to her family doctor’s office on the same day and was diagnosed with Lyme disease. Since Lyme disease can present with symptoms similar to a toothache, dentists should be knowledgeable of the clinical manifestations of Lyme disease. Lyme disease should be considered as differential diagnosis in a patient who presents with compatible symptoms and signs, which may present in the orofacial region.Copyright © 2020. Published by Elsevier Inc.