We report widely disseminated molluscum contagiosum that occurred in a 9-year-old boy secondary to hyperimmunoglobulin E syndrome, a primary immunodeficiency disorder. Cutaneous examination revealed numerous, widespread, skin-colored to translucent, firm, umbilicated papules of varying sizes. They were distributed throughout the perineal and gluteal areas and bilaterally over his lower limbs. A biopsy specimen from his skin lesion demonstrated lobulated epidermal growth that consisted of keratinocytes with large intracytoplasmic eosinophilic inclusion bodies and a central crater. These findings were consistent with the diagnosis of molluscum contagiosum. Many treatments for his skin lesions were ineffective, including physical destruction or manual extrusion of the lesions; cryotherapy; curettage; and topical therapies with phenol, trichloroacetic acid, and imiquimod. The patient was treated successfully with subcutaneous interferon-alpha for 6 months without any adverse effect.