Serologic confirmation is required for diagnosis of Lyme borreliosis in all the patients except those with well confirmed and typical erythema migrans (EM) lesion. In patients with articular symptoms, the primary cause of seronegativity is performing a test at a very early stage of the disease, before detectable levels of anti-Borrelia burgdorferi s.l. antibodies build up. However, recent epidemiologic history and presence of primary skin lesion facilitate diagnosis in most patients at this stage of the infection. Secondly, insufficient antibiotic treatment of EM may halt development of humoral response without total eradication of the pathogen, which may result in the relapse of arthritis without detectable anti-B. burgdorferi s.l. antibodies for up to several months later--a rather rare phenomenon, which, however, must be taken into consideration in patients with a history of treated EM. A fe cases of seronegative Lyme arthritis not related to previous antibiotherapy have been reported, but i seems an extremely rare condition, and, if suspected, should be confirmed by histopathologic or molecular examination of the material from the affected joint.