Treponema pallidum subsp. pallidum (T. pallidum), the etiologic agent of syphilis, can disseminate into virtually any organ including the central nervoussystem (CNS). Among those infected organs, the diagnosis and treatment of central nervous system (CNS) infection is recognised to be the most challenging. If left untreated, neuroinvasion with T. pallidum might lead to asymptomatic meningitis and develop severe even irreversible symptomatic neurosyphilis (NS). In the early 20th century, about 10% of the population of the United States and Europe were infected with syphilis. A century has passed, syphilis still remains a global public health problem, especially in developing countries, such as China, where an estimated 400 thousand people were infected annually in recent ten years.Despite a major health consequence that can cause undue physical, psychological harm and suffering for patients, neurosyphilis has not yet been a priority and remains a medical and public-health problem in many countries. The reasons that the surveillance data of neurosyphilis are limited at global level may because of the following: 1. the Tp invades the CNS in most patients with early syphilis, who may have no symptom at all, which is difficult to determine which patient requires lumbar puncture (LP); 2. the diagnosis of neurosyphilis relies on CSF findings and the laboratory test criteria for diagnosis of neurosyphilis is neither sensitive nor specific; 3.symtomatic neurosyphilis is a “great imitator” and lack of specific clinical manifestations, which may result in misdiagnosis and leaves the disease without treatment for years. Here we reviewed the neurosyphilis in Shanghai Skin Disease hospital, China main land and investigated more than 6000 syphilis patients in Shanghai Skin Disease Hospital. We reinstate the need for LP among syphilis patients, particularly in the settings where syphilis is prevalent among key populations. As the incidence of syphilis continues to increase, further work is needed to better understand neurosyphilis.