Acquired syphilis is contracted through direct sexual contact with ulcerative lesions of skin or mucous membranes of infected people, and has three stages: primary, secondary, and tertiary. Primary syphilis presents with a round, firm, and painless skin ulcer that has a smooth border and a rubbery base. Chancre occurs at the site of contact 10 to 90 days postexposure and heals spontaneously over 3 to 6 weeks. The lesion is usually on the glans penis, cervix, or vagina and less commonly on the lips, nipple, and tongue. Associated painless regional lymphadenopathy may occur 1 to 2 weeks later. Secondary syphilis presents 4 to 10 weeks after the chancre (primary chancre still present in 10% of patients) usually with a rash that is symmetric and generalized on the trunk, extremities, palms, and soles. Lesions vary and may be polymorphic maculopapular annular, papulopustular, psoriasiform, or follicular; the lesions are often copper colored and nonpruritic. A flu-like syndrome, generalized lymphadenopathy, and splenomegaly may also occur as may condylomata lata (highly infectious raised white/gray lesions in warm moist areas like perineal and anal). Some patients have mucous patches in the mouth, alopecia of beard, scalp, or eyebrows. Lesions resolve in 3 to 12 weeks. Tertiary (or late)-stage infection refers to gumma formation (skin, bone, or viscera) and cardiovascular involvement (aortitis). Neurologic infection can occur with any stage of syphilis. Primary and secondary syphilis are sexually transmitted and may be seen in sexually active adolescents. Diagnosis is based on typical skin lesions and confirmed by scraping moist lesions and immediately examining the sample with darkfield microscopy. If a darkfield microscope is not available, a slide of the moist material can be made and sent to a laboratory for staining with specific T pallidum immunofluorescent antibody. The diagnosis of syphilis requires both nontreponemal (eg, RPR) and treponemal (eg, FTA-ABS) testing. Standard testing is usually a nontreponemal screening test followed by a confirmatory treponemal test if positive. Nontreponemal antibody titer correlates with disease activity and usually become nonreactive after treatment. Most patients with reactive treponemal tests will remain positive for their lifetime regardless of treatment or disease activity. RPR is reactive in only about 80% of patients with primary syphilis at presentation, although darkfield microscopy will be positive. Request test with dilutions of serum in order to prevent a false-negative test due to a prozone phenomenon (most common in secondary syphilis with high titers). False-positive nontreponemal test results may occur due to various medical conditions. All patients who have syphilis should be tested for HIV infection. Diagnosis of primary or secondary syphilis in a young child is evidence of sexual abuse and the child needs to be evaluated for other STDs and treated if necessary.