A 6-month-old girl whose parents had recently received a diagnosis of syphilis was referred to the hospital for evaluation and treatment after testing suggested that she also had syphilis. The mother had had a negative result on rapid plasma reagin (RPR) testing early in pregnancy and was not retested at the time of delivery. Ten days before presentation, syphilis was diagnosed in the parents, prompting testing in the infant. The RPR test results were positive (titer, 1:512), and a confirmatory fluorescent treponemal-antibody test was also positive. Physical examination showed frontal bossing and a perirectal mass (Panel A). There was no rash, hepatosplenomegaly, lymphadenopathy, or limitation of limb movement. The perirectal mass had first been noted at 2 weeks of age and was thought to be a hemangioma. A biopsy specimen of the perirectal lesion was obtained, and immunostaining was positive for spirochetes (Panel B). A lateral radiograph of the right tibia showed severe periostitis (Panel C). The child was treated with a 10-day course of parenteral crystalline penicillin, and the perirectal mass decreased in size after treatment (Panel D). The increasing incidence of syphilis in the United States makes the recognition and prevention of congenital syphilis an important public health concern.