A 66-year-old man was admitted for a 7-day history of painful blisters and erosions in the upper lip.Real-time PCR with herpes simplex virus (HSV) type-specific primers showed that the blister fluid and crusts were positive for HSV-1,but negative for HSV-2.Observation of the blister wall with transmission electron microscopy (TEM) revealed 3 types of nucleocapsid in the karyoplast of epithelia cells,including the electron-translucent core,granular core and electron-dense core.Numerous matured viral particles with envelope were found in the cytoplasm,which were identified as HSV.The diagnosis was made as herpes simplex in the upper lip based on the above findings.PCR based molecular typing combined with observation of HSV particles via TEM may be an effective approach to the definite diagnosis of primary herpes simplex.