Abstract Background Cytomegalovirus (CMV) oropharyngeal ulcerations are rare diagnoses that usually only occur in immunocompromised individuals. False-negative third-generation HIV tests in a patient with AIDS are also exceedingly rare and, when they occur, underscore the complex host and viral relationships involved in HIV disease mediation. Case Presentation We present a case of CMV oropharyngeal ulcerations in a patient diagnosed with advanced AIDS with a persistently negative HIV antibody test. Confirmative testing and diagnosis of HIV were performed with a qualitative DNA polymerase chain reaction and confirmed with a quantitative RNA polymerase chain reaction. Cytomegalovirus oropharyngeal ulcerations were managed with ganciclovir 5 mg/kg with significant improvement in oral ulcers. Conclusions We present a rare case of an HIV-seronegative patient clinically diagnosed with advanced AIDS and CMV oropharyngeal ulcerations. False-negative HIV tests can delay diagnosis and treatment; hence, clinical suspicion is needed for accurate diagnosis and early treatment.