Syphilis in preschoolers is rarely described in current medical literature, despite the rise in syphilis in both the adult and the pediatric populations during the past decade. Since that time, 3 children between 3 and 4 years of age have been diagnosed with syphilis at the Children's Hospital of Philadelphia. The presentations and clinical manifestations of syphilis in these 3 children are described, and the difficulty in identifying the source of infection is discussed. The presentations of these children included nephrosis and secondary syphilis, the corymbiform and palmar rash of syphilis, and subtle signs of late congenital infection in an otherwise asymptomatic child. One child had documented congenital infection, 1 had probable congenital infection that went untreated, and 1 did not have appropriate neonatal testing documented. None of the children gave a verbal history of sexual abuse, although it is likely that all three cases resulted from sexual abuse. The evaluation of preschool children with syphilis is confounded by the interpretation of acquired infection in consideration of a history of possible or documented congenital disease. The assessment is complicated further by problems with recognition of clinical disease, the inability of young children to provide a history, prenatal and neonatal testing methods used, changes in treatment recommendations made during the past decade, and inadequate follow-up to document cure of congenitally infected infants. With the increase in syphilis seen in recent years, physicians are more likely to encounter preschoolers with syphilis. Our ability to document acquired infection, however, is hampered by the difficulties encountered in following recommended guidelines for evaluation and follow-up and by limitations in interviewing young victims of sexual abuse, which may impair our ability to protect children from additional harm. Understanding the pathophysiology and progression of this disease remains challenging even in this modern era.