The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, and tertiary). The primary stage classically presents with a single chancre (a firm, painless, non-itchy skin ulceration), secondary syphilis with a diffuse rash which frequently involves the palms of the hands and soles of the feet, latent syphilis with little to no symptoms, and tertiary syphilis with gummas, neurological, or cardiac symptoms. It has, however, been known as "the great imitator" due to its frequent atypical presentations. Diagnosis is usually via blood tests; however, the bacteria can also be visualized under a microscope. Syphilis can be effectively treated with antibiotics, specifically intramuscular penicillin G, and in those who are allergic, ceftriaxone is recommended.

Syphilis is believed to have infected 12 million people worldwide in 1999, with greater than 90 percent of cases in the developing world. After decreasing dramatically since the widespread availability of penicillin in 1940s, rates of infection have increased since the turn of the millennium in many countries, often in combination with human immunodeficiency virus (HIV). This has been attributed partly to unsafe sexual practices among men who have sex with men, increased promiscuity, prostitution and decreasing use of barrier protection.