We report the case of a 21-year-old woman with symmetrically distributed, ulcerated nodules and plaques on the face, neck and arms. Initial differential diagnoses included pyoderma or sarcoidosis based on the clinical presentation and histopathology with non-caseating granulomas. After inefficient treatment with topical and systemic fusidic acid and steroids, we diagnosed nodular secondary syphilis owing to positive serology and immunohistochemical staining of Treponema pallidum in lesional skin. After treatment with benzathine penicillin, skin lesions improved and antibody titres declined significantly within 3 months. Nodular skin lesions in secondary syphilis are rare with 15 reported cases within the last 20 years. Furthermore, the granulomatous histology is often misleading. Our patient's case suggests that the physicians should be aware of syphilis as a possible differential diagnosis also in patients outside a high-risk population for sexually transmitted diseases and with an unusual clinical presentation.