A 34-year-old, HIV-positive man living in Texas presented with a 2-week history of fever, malaise, myalgias, oral ulcers, and papules on his chest, back, face, and extremities, including the palms. Initially secondary syphilis was suspected. However, RPR was negative. Histopathologic examination revealed a lymphocytic infiltrate with numerous intra-histiocytic fungal organisms. GMS and PAS stains were positive, consistent with the diagnosis of histoplasmosis. We report a case of disseminated histoplasmosis clinically mimicking secondary syphilis.