Syphilis is an important public health issue and continues to occur at high rates among HIV-infected patients. Although abnormal liver function tests are common among HIV-infected persons, the incidence of syphilitic hepatitis in this population is currently unknown. We present two cases of syphilitic hepatitis and performed a retrospective study to determine the incidence of hepatitis during early syphilis infections among HIV-infected persons. Our study showed that syphilitic hepatitis is common, occurring in 38% (12/32) of HIV-positive patients with early stages of syphilis infection. Most cases occurred during secondary syphilis, with the most common finding being a maculopapular rash. Syphilis should be included in the differential diagnosis of HIV patients presenting with liver test abnormalities, rash and/or sexual risk factors.