A 62-year-old male presented with a 10-day history of a diffuse, erythematous papular rash sparing the palms and soles. Histopathologic examination of a skin lesion showed loose non-caseating granulomas in a lymphoplasmacytic background. Scattered spirochetes were identified by Treponema pallidum immunohistochemistry, in keeping with a diagnosis of secondary syphilis. Granulomatous inflammation in secondary syphilis is uncommon. A review of the literature reveals that the majority of prior reported cases of granulomatous secondary syphilis share similar characteristics to this case; namely, a papular or nodular clinical presentation, sparing of the palms and soles, and collections of epithelioid histiocytes with associated lymphocytes and variable numbers of plasma cells.