Serology remains the mainstay of diagnosis of syphilis. It's most important issues are: the knowledge of typical and atypical symptoms of the disease, the need of the testing in particular clinical and epidemiological situations, the interpretation of tests' results. The most frequent dilemmas and the relevance of serological tests in congenital syphilis and neurosyphilis, as well as the quality (standardization and reproducibility) of laboratory testing are discussed.