Despite a rapid increase in the number of patients with Lyme neuroborreliosis (LNB), its neuropathological aspects are poorly understood. The objective of this study was evaluation of neuropathological, microbiological, and magnetic resonance imaging (MRI) findings in three patients with the Borrelia burgdorferi infection and neurological disease from whom brain tissue specimens were available. Perivascular or vasculitic lymphocytic inflammation was detected in all specimens. Large areas of demyelination in periventricular white matter were detected histologically and by MRI in one patient. The disease had a fatal outcome in this patient. Brain MRI suggested malignancies in two patients before histopathological studies were carried out. One of these two patients was a child with sudden hemiparesis. Another was a 40-year-old man presenting with epileptic seizures and MRI-detected multifocal lesions, which disappeared after repeated courses of antibiotics. We conclude that cerebral lymphocytic vasculitis and multifocal encephalitis may be associated with B. burgdorferi infection. The presence of B. burgdorferi DNA in tissue samples from areas with inflammatory changes indicates that direct invasion of B. burgdorferi may be the pathogenetic mechanism for focal encephalitis in LNB.