Invasive vulvar carcinoma has been shown to be etiologically heterogeneous on the basis of pathological, virological, and epidemiological criteria. Human papillomavirus-related invasive vulvar carcinoma has basaloid or warty morphology and has adjacent basaloid or warty intraepithelial neoplasia. Invasive carcinoma unrelated to human papillomavirus is a keratinizing squamous carcinoma that may have adjacent squamous hyperplasia. We provided to 3 pathologists for their review and pathological diagnoses stained tissue sections from 95 patients with vulvar carcinoma. The reproducibility for grading individual categories of intraepithelial lesions was only fair (kappa values of 0.31-0.43). The reproducibility was better (moderate to good; kappa values of 0.58-0.59) for grading individual categories of invasive carcinomas. The agreements improved when the basaloid and warty categories were combined. Good agreement was achieved (kappa values of 0.55-0.79) in distinguishing human papillomavirus-related lesions from those unrelated to human papillomavirus; all three reviewers agreed on this classification for 67% of the cases. The intrareviewer agreement was of the same order as interreviewer agreement. Difficulties in differentiating between some lesions (e.g., a warty carcinoma with little atypia from a well- to moderately differentiated keratinizing squamous carcinoma) and concurrent occurrence of human papillomavirus-related lesions and those lesions unrelated to human papillomavirus in a patient may account for some of the discrepancies in the histopathological diagnoses of vulvar carcinoma.