BACKGROUND: Pemphigus vulgaris (PV) is an autoimmune disease characterized by blistering of the skin and mucosa, which develops due to the interaction between predisposing genetic and environmental factors. Infections caused by members of the Herpesviridae family have been suggested as a possible triggering factor for PV. OBJECTIVE AND METHODS: In this report, we investigate the presence of herpesviruses in refractory lesions on the right upper eyelid. The lesion has persisted despite the treatment with corticosteroids. Polymerase chain reaction (PCR) and DNA sequence analysis have been used to detect the DNA of HSV 1/2, VZV, EBV, CMV, HHV-6, HHV-7, and HHV-8. RESULTS: The sample collected from the right upper eyelid has tested positive for HSV 1/2. Sequence analysis has confirmed the PCR results and allowed the identification of the HSV strain as belonging to type 1. After treatment with acyclovir, the lesion of the right upper eyelid has cleared and not relapsed. CONCLUSION: When patients present PV lesions which are refractory to corticosteroid therapy, herpetic infection should be considered.