The management of an HIV-infected patient with syphilis is an evolving and difficult area of clinical medicine. Many such patients initially present with dermatologic problems, and the practicing dermatologist must be alert to the variety of presentations syphilis may take in these patients. The role of biopsy with immunofluorescent or Warthin-Starry silver staining is often crucial in correctly diagnosing confusing cases. The treatment of early syphilis in HIV-infected patients may need to be more intensive than has previously been recommended, because the immunosuppression induced by HIV can accelerate the pace of the infection and increase the risk of progression to neurosyphilis. After treatment, careful and frequent follow-up is essential so that the often irreversible consequences of late syphilis can be avoided.