Background: Vulvar cancer is a relatively rare gynecologic malignant disease. The majority of these tumors are vulvar squamous cell carcinoma (VSCC). There are two distinct aetiopathogenic pathways leading to VSCC: human papillomavirus (HPV)-dependent and HPV-independent. The precursor lesions of HPV-independent VSCC include differentiated vulvar intraepithelial neoplasia(VIN), vulvar acanthosis with altered differentiation(VAAD) and differentiated exophytic vulvar intraepithelial lesion(DE-VIL) . To date, the report of DE-VIL has not been found after this term was proposed in 2017. So it usually has been under-recognised by pathologists in the past owing to the incidence of DE-VIL is relatively small.Case presentation: Here, we report a typical case of DE-VIL, which exhibits the absence of HPV infection and mutations in TP53. Interesting, a small lesion showed similar morphologic feature to HSIL nearby the lesion of DE-VIL.However, it showed same immunochemical patterns with DE-VIL. To date, no other study has reported this phenomenon. Whether it is a rare subtype of DE-VIL or only a accompanying status is still unclear.Conclusions: As the precursor lesions of HPV-independent VSCC, DE-VIL was too difficult to diagnosis due to the lack of sufficient evidence. Therefore, we should pay more and more attention for DE-VIL.