Castleman's disease (CD) is an unusual massive proliferation of lymphoid tissue distinct in two clinical forms, localized and multicentric. The multicentric form has been related to human herpesvirus 8 (HHV-8), especially in HIV-infected patients, whereas the localized form of CD is still unrelated to viral pathogens. We report a case of a HIV-negative 16-year-old male referred to our hospital with a 12-month history of a painless swelling in his right parotid region. A parotidectomy was performed, and histological analysis evidenced a localized CD. The search for HHV-8 revealed an active virus infection. The patient was commenced on corticosteroid therapy and a follow-up was performed every 6 months. The patient was commenced on corticosteroid therapy and there has been no recurrence after 24 months. The authors report a case of localized parotid CD in a patient with evidence of an active HHV-8 infection. The results of this study does for the first time suggest an association between HHV-8 and localized CD in HIV-negative subjects.