Vulvar squamous carcinoma is an uncommon neoplasm that afflicts a spectrum of women and has been associated with granulomatous vulvar diseases, papillomaviruses, and chronic inflammatory disorders of the vulva. Histopathological, molecular, and epidemiological studies have revealed two subsets of vulvar squamous neoplasia, which are distinguished by their association with human papillomaviruses and patient demographics. This review summarizes the evidence both supporting the diverse pathogenesis of these tumors and the existence of factors that may be common to both groups. Ultimately, the pathway to both human papillomavirus positive and negative vulvar cancers may involve not only obvious precancerous changes but also biological events in the vulvar mucosa that precede the onset of morphological atypia.