“Leukoplakia-like” plaque on the tongue is an uncommon skin manifestation of secondary syphilis. Skin lesions of secondary syphilis usually have numerous presentations, which mimic many other skin diseases, especially in the presence of HIV co-infection. Oral hairy leukoplakia (OHL) is characterized by corrugated whitish patches and plaques on the lateral border of the tongue. It is frequently and strongly associated with HIV but may appear in other diseases. A 47-year-old man with HIV and receiving HAART therapy developed a leukoplakia-like plaque on the tongue, which was first suggestive of OHL but was eventually diagnosed as secondary syphilis.