During the past decade, the role of human papilloma virus (HPV ) in the pathogenesis of gynecologic cancer in both genders has been elucidated. There are five main types of cancer that affect a woman’s reproductive system: cervical, ovarian, endometrial, vaginal, and vulvar. A sixth rare type of gynecologic cancer, fallopian type, completes the spectrum of female gynecologic malignancies. This chapter reviews the five major female gynecologic cancers as well as trophoblastic disease, and addresses how primary care clinicians can increase primary prevention, overcome diagnostic challenges, and improve utilization of gynecologic cancer screening. The most common histologic types of cervical cancer are squamous cell and adenocarcinoma. Hormonal, genetic, and environmental factors have all been identified as playing a role in the development of ovarian cancer. Tumors of the uterine fundus represent the most common group of gynecologic malignancies.