Erythema multiforme is a widespread hypersensitivity reaction, its pathogenesis is related to a variety of factors, including drugs and viral and bacterial infections. It is true that erythema multiforme is often caused by viruses while current studies suggest that it is mostly associated with herpes simplex virus infection, rarely associated with varicella-zoster virus infection. Here, we report a 50-year-old man admitted to our hospital because of rashes on the left rib with pain for 9 days and on limbs and hands for 2 days. Laboratory data showed that varicella-zoster virus (VZV-DNA) test was negative in blood by qualitative polymerase chain reaction. Herpes zoster virus IgM (VZV-IgM) enzyme linked immune sorbent assay was negative, and herpes zoster virus IgG (VZV-IgG) enzyme linked immune sorbent assay was positive. Herpes zoster and erythema multiforme was diagnosed. After treatment with antiviral, antiallergic, and topical drugs, the rashes was significantly improved. Our case report contributes to the pathogenesis of erythema multiforme.