Vulvar and vaginal cancers are rare and predominantly involve squamous cell carcinomas. Some studies combine these cancers, presumably because of their rarity, anatomic proximity, and shared risk factors. Major risk factors include human papillomavirus (HPV) and cigarette smoking. This chapter explores the similarities and important differences in etiology between these cancer sites. In addition to its focus on invasive cancer, the chapter also discusses high-grade precursor lesions, or in situ disease, that sometimes progress to cancer and must, therefore, be treated.