Establishing a diagnosis of syphilis, whatever the stage of the disease, can be difficult because syphilis is a great mimic in clinical morphology and histology. Many patients infected with venereal diseases have oral manifestations, but very few dentists and physicians have the proper experience to diagnose syphilis or other STDs from oral lesions. Oral secondary syphilis appears to be very uncommon, and few cases have been reported over the recent past. We present 4 patients who developed secondary syphilis-related oral lesions of moist ulcers, irregular linear erosions termed 'snail-track' ulcers, or erythematous mucous patches on the labial mucosa, buccal mucosa, palate, or tongue. Concurrent human immunodeficiency virus (HIV) infection was diagnosed in 1 patient. The histological examination in 2 patients showed dense subepithelial inflammatory cell infiltration comprised predominantly of plasma cells, and it was of practical help in the diagnosis of syphilis. The diagnostic value of a histological examination, serologic tests, and treatment of syphilis are discussed. Obviously, coinfection with HIV will complicate the clinical presentation, diagnosis, and management of syphilis. Concurrent HIV infection should be considered in any patient with a sexually transmitted disease including syphilis.