Genital ulcer disease is a common presentation of sexually transmitted infections (STIs) and can cause significant morbidity in patients. Syphilis (chancre of primary syphilis) and genital herpes are the two most significant ulcerative STIs and are occasionally indistinguishable clinically. Infectious syphilis is on the rise in Singapore particularly in men who have sex with men (MSM); whilst genital herpes although showing a decreasing incidence in recent years still presents with more than 500 notifications a year as first episode genital herpes. Due to the breaks in the mucosa of the skin caused by the ulcers, the risk of acquisition as well as transmission of HIV infection are both increased making timely treatment of genital ulcers of utmost importance. Although uncommon in Singapore, chancroid, LGV and granuloma inguinale remain endemic in some parts of Asia and there should be a high index of suspicion for patients who have returned from these regions presenting with ulcerative lesions. All patients who present with genital ulcers should have their blood tested for syphilis and HIV as well as a swab for culture or PCR testing taken from the ulcer to exclude genital herpes.