Clinicians involved in the diagnosis of mucocutaneous diseases should be aware that syphilis is still prevalent among humans and its accurate diagnosis may require substantial clinical evaluation. Herein, we report a case of primary syphilis presenting as an isolated ulcer on the upper left labial oral mucosa. The lesion exhibited no specific features and could have been easily mishandled. An important clinical observation was the presence of a satellite-enlarged lymph node in the left submandibular area, which was highly indicative of primary syphilis. Histopathological examination of the specimen obtained by punch biopsy revealed features suggestive of syphilis and immunohistochemical staining with antitreponemal antibody confirmed its diagnosis with the detection of numerous Treponema pallidum in the specimen.