Granulomatous inflammation in secondary syphilis is rare and poses diagnostic challenges both on clinical grounds and histologically. We report a case of granulomatous syphilis in a 44-year-old woman that presented with an erythematous papulo-nodular rash involving her face, neck and upper portions of chest, back and arms that was initially diagnosed as urticaria and treated ineffectively with systemic steroids. No mucosal or genital lesions, involvement of soles and palms, or lymphadenopathy was present. Histopathologic examination revealed dense dermal perivascular and periadnexal inflammatory infiltrate composed of lymphocytes and plasma cells accompanied by prominent granulomatous inflammation. Anti-treponemal immunohistochemical study revealed spirochetes and along with positive serology, supporting the diagnosis of secondary syphilis. With an increasing number of reported syphilis cases recently, internists, infectious disease specialists, dermatologists and dermatopathologists alike should be aware of the unusual presentations of this great imitator. We also present a review of literature of cases of secondary syphilis that present in such unusual clinical and histologic phenotypes.