Malignant syphilis is a rare manifestation of secondary syphilis. It is characterized by papulopustular skin lesions that rapidly enlarge and evolve into round or oval ulcers with sharp borders centrally covered by a dark - sometimes rupioid - crust. The diagnosis is typically established by strongly positive serological tests a severe Herxheimer reaction and an excellent response to antibiotic therapy. Most reported cases of malignant syphilis are described in association with HIV infection. Patients co-infected with syphilis and HIV are also at risk for developing neurosyphilis. Penicillin remains the treatment of choice in all stages of syphilis. A 19-year-old woman presented to the Hospital de Clinicas a tertiary care center at the Federal University of Parana with aggressive skin and mucous membrane lesions and complaints of fever weight loss and malaise. The lesions had started exclusively in the patients mouth a few weeks prior and had since developed over her face thorax back and whole body. Physical examination revealed dry encrusted non-bleeding pruritic lesions disseminated over the patients body. Severe lesions on her back covered all possible puncture sites for collection of cerebrospinal fluid. The womans axillary temperature was 38.0 °C her blood pressure was 110/70 mm Hg and her pulse rate was 80 beats per minute. The patient refused to undergo a gynecologic exam. The clinical laboratory results were a positive Venereal Disease Research Laboratory (VDRL) test (dilution 1:128) with a positive FTA-ABS test a positive enzyme-linked immunosorbent assay (ELISA) HIV serology test followed by a Western blot confirmatory analysis. CD4+ cell count was 134/mm3 which characterized a co-infection of HIV and syphilis. Serological examination for hepatitis B and C showed negative results. A skin lesion biopsy was performed and confirmed secondary syphilis. Because it was impossible to test the patients spinal fluid and the extent of her clinical symptoms treatment with penicillin for neurosyphilis was started promptly. The patient received 3million units of intravenous penicillin G at 4 hour intervals for 14 days. The Jarisch-Herxheimer reaction occurred during the first penicillin administration. Treatment with dipirone produced satisfactory results. Highly active antiretroviral therapy (HAART) with a triple combination of lamivudine (3TC) zidovudine (AZT) and nelfinavir was started concomitantly as was prophylactic treatment with sulfamethoxazole-trimethoprim. After 2 weeks the patients lesions had regressed remarkably and she was discharged from the hospital with HAART and prophylactic sulfamethoxazole-trimethoprim therapy. The patient continued to respond positively to the treatment with a complete remission of the lesions. At the 2 follow-up visits (30 and 90 days later) only disseminated dischromic patches could be seen as sequela. The course of syphilis is often atypical or dramatic in HIV seropositive patients and other authors have also described its unusually aggressive dermatological manifestations. The classical clinical picture of malignant syphilis was diagnosed in the present case. HIV co-infection made the secondary stage of syphilis more aggressive and altered the natural course of the disease: lesions had a fast progression and disseminated over the whole body in a few days including the mouth and other major areas. Because the patient was immunocompromised by HIV she had a significantly higher likelihood of developing neurosyphilis. Secondary syphilis can have a more aggressive course in HIV-infected patients who develop malignant syphilis. The possibility of neurosyphilis should be promptly investigated. If testing is not possible as in the present case the patient should be presumptively treated for neurosyphilis. The lesions will typically respond rapidly to penicillin. (full-text)