The definitive diagnosis of acute neuroborreliosis (NB) is based upon the presence of lymphomonocytic CSF pleocytosis and intrathecal Borrelia burgdorferi (B.b.)-specific antibody production (expressed by an antibody index of >2). However, the latter might be absent in early stages of the disease. Now a recently discovered additional CSF marker-the cytokine CXCL13-was found to be positive in every initial CSF sample from patients with NB and therefore could be a valuable tool for early diagnosis and initiation of antibiotic therapy. We report an unusual case of NB in a patient with a history of metastatic carcinoma of the prostate and unilateral polyradiculitis. While no intrathecal B.b.-specific antibody production could be demonstrated initially, the CSF CXCL13 level was high (>500 ng/g vs <1.7 ng/g in healthy controls). During the course of the disease, the antibody index turned positive (4.8) and the patient responded to antibiotic therapy, thus confirming the diagnosis. In this case, measuring CXCL13 in the CSF would have led to earlier diagnosis and treatment of NB.