ABSTRACT Leucoderma syphiliticum (LS), originally described as syphilide pigmentaire, encompasses a spectrum of dyschromic lesions that emerge during the course of secondary syphilis. Very few case reports are available in modern biomedical databases. We present the case of a 57-year-old HIV-infected male patient who presented with several round to oval, non-scaling, slightly raised and well-demarcated hypochromic lesions scattered over the trunk, abdomen, dorsum, and arms. Prior non-treponemal tests were negative for syphilis, but novel studies yielded positive results at high titers. Skin lesions slowly regressed and the hypochromic areas repigmented a few weeks after benzathine penicillin G treatment. This is the first report of LS in an HIV-infected patient. A review of modern and ancient literature was performed. The present case report emphasizes the need for clinicians to have a heightened awareness of the varied and unusual clinical phenotypes of syphilis.