In recent years, increase in the incidence of neurosyphilis (NS) was observed in the Russian Federation, often leading to disability and death. Laboratory techniques for NS diagnosis approved in the Russian Federation (RF) are in some cases incapable of diagnosing the disease, which necessitates the development of new diagnostic approaches. Objective — the study was aimed at the comparative analysis of standard methodologies that were not previously used in the Russian Federation in the diagnosis of NS. Material and methods. Paired samples of serum and cerebrospinal fluid (CSF) from 65 patients with NS and other forms of syphilis were studied. NS was diagnosed by examining the samples using approved clinical, biochemical, and immunochemical methods, as well as by calculating ITPA-index (Intrathecal Treponema pallidum assay), which was not previously used in the RF. Results. The study demonstrated higher effectiveness of ITPA-index in the diagnosis of NS and other forms of syphilis compared to the complex of methodologies approved in the Russian Federation (non-treponemal and treponemal immunochemical tests, study of protein levels and cell count in the CSF). Assessment of the index enables diagnosing NS in the absence of pleocytosis, hyperproteinarchia, positive non-treponemal test values, as well as low index of Treponema pallidum immobilization in the CSF. Conclusions. High effectiveness of ITPA-index suggests that this method may be recommend for the diagnosis of NS and verification of other forms of syphilitic infection.