The use of PET/CT for determining systemic Kaposi sarcoma (KS) involvement and treatment response remains to be formally assessed. Pretreatment human herpes virus-8 (HHV-8) viral load may predict clinical response of KS to therapy; however, its role in treatment monitoring and correlation with PET/CT findings is unknown. We report PET/CT findings and HHV-8 viral loads of a 46-year-old man with HIV-associated lymphadenopathic KS. After treatment with highly active antiretroviral therapy, an interval PET/CT showed partial response, despite an undetectable HHV-8 viral load. Chemotherapy was initiated, and the patient achieved a complete clinical, PET/CT, and virological response. PET/CT enabled monitoring of treatment response and led to changes in management.