Vulvar squamous cell carcinoma (VSCC) is the most common carcinoma of the female external genitalia, and the incidence of VSCC and its pre-neoplastic lesion, vulvar intraepithelial neoplasia (VIN), have been increasing. Unlike cervical and anal squamous cell carcinomas, which are nearly all HPV-associated, many vulvar VSCC are HPV-independent. As a group, the HPV-independent VSCC differ from the HPV-associated VSCC with respect to age at diagnosis (older), morphology (well-differentiated keratinizing vs. basaloid or warty), associated pathology (lichen sclerosus), precursor lesions (HPV-independent VIN vs. HSIL) and prognosis (worse). In effect, the HPV-associated and HPV-independent VSCC are different diseases. However, significant clinical and morphologic overlap exists between the two types. Each type of VSCC arises in the background of a specific intraepithelial precursor: HPV-associated carcinomas arise from high-grade intraepithelial lesions (HSIL), formerly referred to as vulvar intraepithelial neoplasia of usual type (uVIN) or classic VIN, whereas HPV-independent VSCCs frequently arise in a background of lichen sclerosus (LS). HPV-independent VIN includes those lesions previously described as differentiated VIN, vulvar acanthosis with altered differentiation (VAAD), and differentiated exophytic vulvar intraepithelial lesion (DEVIL), and is arguably the most difficult diagnosis to make in gynaecological pathology. It is under-recognized in clinical practice. Most cases of HPV-independent VIN are associated with abnormal p53 expression and TP53 mutation. Recently there has been increasing appreciation of the less common p53 wild type, HPV-independent VIN. The VSCC arising from p53 wild type HPV-independent VIN are very well differentiated and have a prognosis that is more favorable than p53 mutant HPV-independent VSCC. This presentation will focus on diagnosis of VSCC and its precursor lesions, and highlight how this impacts on treatment and patient outcomes.