Vitiligo is an idiopathic skin disorder of multifactorial etiology that is characterized by skin depigmentation. Generalized vitiligo following radiation therapy has rarely been reported in the literature. The mechanism underlying radiation-induced disseminated vitiligo is not yet fully understood. However, multiple factors, including genetic susceptibility and autoimmunity, are likely involved in the pathogenesis of the condition. We report a case of disseminated vitiligo in a patient with no preexisting personal or family history of the condition following three months of localized radiation therapy to the mediastinum.