Hyperimmunoglobulin E syndrome (HIES) or Job's syndrome is a rare immunodeficiency disease with less than 200 cases reported worldwide, among which few cases are reported with lesions due to herpes simplex virus (HSV) or human papillomavirus (HPV). This case study presents a rare case of HIES with coinfection of HSV and HPV. A 12-year-old boy, previously diagnosed with HIES, presented with a large conjunctival mass lesion. The presence of HPV in the lesion was confirmed by biopsy and by using the line-probe assay method to detect the HPV genome. However, the mass lesion did not respond to anti-HPV therapy with topical interferon-α2b (IFN-α2b) and oral cimetidine but improved promptly after intravenous (IV) acyclovir, which is often administered for cutaneous herpetic lesions. This suggested the presence of HSV in the conjunctival mass. Review of pathology and HSV immunohistochemical staining confirmed the presence of HSV as a coinfection. The likelihood that the mass arose from an abnormal host response to HSV and HPV due to HIES was considered, but coexisting infection with these two viruses and HIES has not been reported in the literature; therefore, such cases require further investigation.