Syphilis is a disorder that may mimic many other diseases. Its incidence has risen and fallen over the centuries. A particularly malignant and virulent form, lues maligna, has recently been more frequently observed in the HIV-infected population. Raising the awareness of the occurrence of and the clinical and laboratory criteria of syphilis in general and lues maligna in particular in the HIV-infected population is becoming more urgent. Early treatment can result in a good outcome and stem the spread of the disease; as with other forms of syphilis, penicillin is the drug of choice.