Syphilis () is a sexually transmitted infection caused by the bacterium Treponema pallidum subspecies pallidum. 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 usually between 1 cm and 2 cm in diameter) though there may be multiple sores. In secondary syphilis, a diffuse rash occurs, which frequently involves the palms of the hands and soles of the feet. There may also be sores in the mouth or vagina. In latent syphilis, which can last for years, there are few or no symptoms. In tertiary syphilis, there are gummas (soft, non-cancerous growths), neurological problems, or heart symptoms. Syphilis has been known as "the great imitator" as it may cause symptoms similar to many other diseases.

Syphilis is most commonly spread through sexual activity. It may also be transmitted from mother to baby during pregnancy or at birth, resulting in congenital syphilis. Other diseases caused by Treponema bacteria include yaws (T. pallidum subspecies pertenue), pinta (T. carateum), and nonvenereal endemic syphilis (T. pallidum subspecies endemicum). These three diseases are not typically sexually transmitted. Diagnosis is usually made by using blood tests; the bacteria can also be detected using dark field microscopy. The Centers for Disease Control and Prevention (U.S.) recommend all pregnant women be tested.

The risk of sexual transmission of syphilis can be reduced by using a latex or polyurethane condom. Syphilis can be effectively treated with antibiotics. The preferred antibiotic for most cases is benzathine benzylpenicillin injected into a muscle. In those who have a severe penicillin allergy, doxycycline or tetracycline may be used. In those with neurosyphilis, intravenous benzylpenicillin or ceftriaxone is recommended. During treatment people may develop fever, headache, and muscle pains, a reaction known as Jarisch–Herxheimer.

In 2015, about 45.4 million people had syphilis infections, of which six million were new cases. During 2015, it caused about 107,000 deaths, down from 202,000 in 1990. After decreasing dramatically with the availability of penicillin in the 1940s, rates of infection have increased since the turn of the millennium in many countries, often in combination with human immunodeficiency virus (HIV). This is believed to be partly due to increased sexual activity, prostitution, and decreasing use of condoms.