After a marked decline in the number of syphilis cases in the context of AIDS prevention campaigns, a significant increase has been observed in states of the former Soviet Union since 1994. In recent years, outbreaks have also been reported in the US, Canada, and several European countries. The current epidemic in the US and in different parts of Europe has largely involved men who have sex with men, many of whom are infected with HIV. Since a misdiagnosis of syphilis can have serious consequences for the patient and also for pregnancies and newborns, clinicians should be aware of the many manifestations of syphilis and difficulties in the diagnosis and management of the disease. Younger clinicians in particular are no longer familiar with the diverse clinical symptoms and the complex diagnostics of syphilis. Patients co-infected with HIV may present with atypical clinical manifestations and laboratory test results. Furthermore, through its association with an increased risk of HIV infection, syphilis has acquired a new potential for morbidity and mortality, and the diagnosis of syphilis should be routinely considered in patients with uveitis, sudden deafness, aortic thoracic aneurysm, or pregnancy. Only a minority of syphilis infections are detected in the primary stage. This may be because of atypical locations and, occasionally, atypical morphology of the lesions; however, it may also be because of the difficulty of detecting the pathogen. In the secondary stage, which is clinically extremely diverse, the diagnosis is confirmed serologically. There is a need for increased awareness of the symptoms and signs of acute infections, together with a willingness to consider the diagnosis of syphilis in patients with vague symptoms. An increasing number of diagnostic tests (both specific and nonspecific) are now available. However, in the absence of clinical symptoms or in cases with a low titer or inconsistent test results, diagnosis of syphilis can be difficult or even impossible. Treatment and follow-up should follow current guidelines designed for the involved area. In this article, the cutaneous manifestations of syphilis and their diagnostic and therapeutic management are described in detail.