Abstract Peripheral neuropathy is a recognized but incompletely understood manifestation of borreliosis. As the pathology of this neuropathy has been described only in small case series, the value of nerve biopsy findings for the pathologic diagnosis of Borrelia-associated neuropathy is unclear. We collected and investigated 21 patients with peripheral neuropathy and with typical clinical and serologic signs of neuroborreliosis [Borrelia neuropathy (BN)]. Standard histology and immunohistochemistry were performed on sural nerve biopsies using antibodies to CD4, CD68 and membrane attack complex C5b-9, intercellular adhesion molecule (ICAM)-1, tumor necrosis factor (TNF)-α, interleukin (IL)-1, and IL-6. Nine patients with idiopathic vasculitic neuropathy (VN) and 14 with idiopathic axonal neuropathy (AN) served as disease controls. In BN, the characteristic histology was that of an AN with transmural or perivascular lymphocytic infiltration of nerve vessels. In BN, but less in VN and AN, perineurial thickening and neovascularization were observed. For BN but not for VN, this thickening correlated with increased perineurial immunoreactivity (IR) to TNF-α, C5b-9, and ICAM-1. In comparison to AN, both BN and VN displayed increased perineurial T-cell infiltration and human leukocyte antigen (HLA)-DR3-IR. In the endoneurium, cytokine (IL-1β, IL-6, TNF-α), HLA-DR3, and ICAM-1 expression was more pronounced in VN but not in BN. The neuropathy in patients with neuroborreliosis resembles idiopathic VN but shows some distinctive features. None of the findings of this study are disease specific but as a pattern may help support the diagnosis of inflammatory neuropathy in patients with serological evidence for Borrelia infection.