Syphilis is an infectious and sexually transmitted chronic disease caused by Treponema pallidum. The progression of syphilis is classified into early symptomatic (primary, secondary, early latent) and late asymptomatic (late latent, tertiary) stage. Since the late 20th century, resurgence of infectious syphilis have been occuring among hetero- and homosexual males with HIV co-infection over the world, and similar trend can also be observed in Korea. In order to contain the current spread of syphilis, clinical presentation and diagnostic approach must first become available, and in particular, the peculiarity in HIV co-infection should also be considered. Serology remains the mainstay of laboratory testing for syphilis, except for during the very early stage of infection. If syphilis patients are not diagnosed properly, it may lead to a serious public health problem. Based on the review of literatures, RPR/VDRL test is not reliable as a single screening test, and a new syphilis test algorithm of treponemal antibody test needs to be established as a primary screening test.