The screening for syphilis during pregnancy is important to prevent intrauterine transmission and complications. Prozone phenomenon may cause a false negative result in non-treponemal syphilis tests, which complicates an accurate diagnosis. In this case report a newborn syphilis case was presented to emphasize the importance of reverse algorithm in diagnosis and the prozone phenomenon which can cause problems in rapid plasma reagin (RPR) test. The 2920 g infant patient was born from a 24-year-old mother with no known diseases, at the 35th week of gestation by cesarean section due to premature rupture of membranes. The initial physical examination of the newborn revealed erythema and exfoliation of the bilateral hands and feet. Laboratory results revealed CRP: 90 mg/L, WBC: 19.2 x 103/µl, hemoglobin: 9.5 g/dl, platelet count: 214 x 103/µl, HIV-Ag/Ab: non-reactive, anti-Toxoplasma gondii IgM and IgG: negative, anti-cytomegalovirus IgM: negative, anti-cytomegalovirus IgG: positive (128.7 AU/ml), anti-Rubella IgM: negative, anti-Rubella IgG: positive (26 IU/ml), anti-Treponema pallidum (anti-T.pallidum) antibody [IgM and IgG by the chemiluminescence microparticle enzyme immunoassay (Architect Syphilis TP; Abbott Japan Co, Japan)]: positive (Signal Cut Off value (S/CO): 28.35), and RPR (Omega Diagnostics, UK): negative. All of the above ELISA tests were performed by using Architect (Abbott Diagnostics, Wiesbaden, Germany) kits. When the RPR test was repeated with serial dilutions of the serum in order to detect prozone phenomenon, positive reaction was detected starting from 1:2 and ending at 1:64 dilution. It was determined that the mother was not tested for syphilis during her pregnancy. When both the mother and the father were tested for syphilis, the mother's anti-T.pallidum total antibody test result was reactive (S/CO: 30.52) and the RPR was positive at 1:32 dilution, while the father's anti-T.pallidum total antibody test result was reactive (S/CO: 16.05) and the RPR was negative. A four-fold difference between the maternal and infant RPR dilutions is required by the guidelines for a laboratory diagnosis of congenital syphilis. Although this criterion was not met in the newborn, the case was accepted as congenital syphilis due to clinical findings. Congenital syphilis must be considered in the differential diagnosis in the presence of skin manifestations at the birth and early neonatal period. Accurate and early diagnosis of the disease is important to start appropriate treatment and prevent complications. As described in the presented case, the use of reverse syphilis test algorithm will enable to reach the correct diagnosis of the infection. If the result of the treponemal test is positive and the RPR test is negative, prozone phenomenon should be considered and the RPR test should be repeated with serial serum dilutions.