Introduction: In USA, the incidence of syphilis was declining for the past several years, recently because of HIV infection, the rate of primary and secondary syphilis is gradually increasing. HIV and syphilis affects similar patient groups and co-infection is common. Syphilis may present with nontypical features in the HIV patient. Case Description: A 58-year-old African American female presented with unintentional weight loss, generalized body rash involving palms and soles associated with hair loss of two months duration. She has history of multiple sexual partners, unprotected sex and prostitution. Skin examination showed widespread papulonodular and ulcerated lesions. The lesions were wide spread, involving palms and soles. She also has thin, fragile scalp hair and scalp hair loss without genital ulceration; other system examination was benign. Patient found to be reactive for HIV antigen with HIV-1 genotype. CD4 count was 126. Rapid plasma reagin was 1:128. Treponema Pallidum antibody was reactive. Discussion: Generally, syphilis presents in HIV infected patients similar to general population yet with some difference. Diagnosis is based on serologic test and microbiology. For serology, both non treponemal antibody test, and specific treponemal antibody test can be used. Secondary syphilis in patient with HIV has varied skin presentation, which can mimic cutaneous lymphoma, mycobacterial infection, bacillary angiomatosis, fungal infections or Kaposi’s sarcoma. In our patient, she was having diffused maculopapular rash, involving palms and soles, significant hair loss, positive serology, and skin finding. She was treated for secondary syphilis with benzathine penicillin. In newly diagnosed HIV, patients should be screened for other sexually transmitted infections, including syphilis.