Lyme disease, or borreliosis, is a zoonosis transmitted by Borrelia burgdorferi which also involves the central nervous system (CNS), in 15% of affected individuals, with the occurrence of aseptic meningitis, fluctuating meningoencephalitis, or neuropathy of cranial and peripheral nerves. Encephalopathy with white matter lesions revealed by magnetic resonance imaging (MRI) scans in late, persistent stages of Lyme disease has been described. In this report, we describe a patient with few clinical manifestations involving exclusively the eighth cranial nerve, monolaterally and diffuse bilateral alterations of the white matter, particularly in the subcortical periventricular regions at cerebral MRI. This single patient study shows that the search for antibodies against Borrelia burgdoferi should always be performed when we face a leukoencephalopathy of unknown origin. An isolated lesion of the eighth cranial nerve can be the only neurologic sign in patients with leukoencephalopathy complicating Lyme disease.