Syphilis, caused by Treponema pallidum, can mimic infections like chickenpox and mpox, especially in patients with HIV, making diagnosis challenging. This case involved a 30-year-old HIV-positive man who presented with fever, sore throat, and widespread rash. He was initially suspected to have a viral illness and was therefore treated with acyclovir. However, his symptoms did not improve, so further tests were performed. PCR analysis of skin and lymph node biopsies confirmed T. pallidum as the causative agent. The patient had a known penicillin allergy and was therefore treated with doxycycline, which resolved his symptoms. Secondary syphilis often presents with diverse symptoms, including skin rashes, lymphadenopathy, and oropharyngeal involvement, which can easily be mistaken for other infections. This case emphasizes the importance of considering syphilis in the differential diagnosis of HIV patients with similar symptoms and highlights the critical role of PCR testing in providing an accurate diagnosis and guiding appropriate treatment.