A 44-year-old man presented with visual field defects. Ophthalmoscopy revealed papilloedema of the left eye. Neuroborreliosis was suspected and serum was positively being tested using VIDAS* Lyme screen II (bioMerieux Vitek Inc). However, confirmatory testing using the Borrelia VlsE C6 titre was negative. Western Blotting on serum and cerebrospinal fluid could not confirm the possible diagnosis of neuroborreliosis. VDRL and TPPA testing was positive, and finally, the diagnosis of neurosyphilis was established. We subsequently screened our database on patients with positive VIDAS Lyme screening and negative confirmatory testing by Western blot, and found another 5 cases in which Lyme screening was false positive due to cross-reactivity with Treponema pallidum antibodies. Our data show that in patients with positive Lyme screening and negative confirmatory testing, performance of lues serology should be considered.