Due to diverse clinical and histopathological presentations, diagnosis of secondary syphilis can occasionally prove challenging. Variable clinical presentations of secondary syphilis in HIV disease may result in an incorrect diagnosis and an inappropriate treatment regimen. Similarly, the histology of secondary syphilitic lesions may show considerable variation, depending on the clinical morphology of the eruption. We report a case of secondary syphilis in an HIV infected patient with cutaneous palmoplantar lesions simulating palmoplantar psoriasis.