Vaginal cancer is a malignant tumor that forms in the tissues of the vagina. Primary tumors are most usually squamous cell carcinomas. Primary tumors are rare, and more usually vaginal cancer occurs as a secondary tumor. Vaginal cancer occurs more often in women over age 50, but can occur at any age, even in infancy. It often can be cured if found and treated in early stages. Surgery alone or surgery combined with pelvic radiation is typically used to treat vaginal cancer. Children can be diagnosed with advanced vaginal cancer. They are treated by surgery, radiation therapy, and chemotherapy. Vaginal cancer in children may recur. Gene therapy to treat vaginal cancer is currently in clinical trials.

Squamous-cell carcinoma of the vagina arises from the squamous cells (epithelium) that line the vagina. This is the most common type of vaginal cancer. It is found most often in women aged 60 or older. Vaginal adenocarcinoma arises from the glandular (secretory) cells in the lining of the vagina. Adenocarcinoma is more likely to spread to the lungs and lymph nodes. Clear cell adenocarcinoma occurs in a small percentage of women (termed "DES-Daughters") born between 1938 and 1973 (later outside the United States) that were exposed to the drug diethylstilbestrol (DES) in utero. DES was prescribed to 5 to 10 million mothers period to prevent possible miscarriages and premature births. Typically, women develop DES-related adenocarcinoma before age 30, but increasing evidence suggests possible effects or cancers (including other forms of vaginal glandular tumors) at a later age. DES-exposure in women is also linked to various infertility and pregnancy complications. Daughters exposed to DES in utero may also have an increased risk of moderate/severe cervical squamous cell dysplasia and an increased risk of breast cancer. Approximately one in 1,000 (0.1%) DES Daughters will be diagnosed with clear cell adenocarcinoma. The risk is virtually non-existent among premenopausal women not exposed to DES. Vaginal germ cell tumors (primarily teratoma and endodermal sinus tumor) are rare. They are found most often in infants and children. Sarcoma botryoides, a rhabdomyosarcoma also is found most often in infants and children. Vaginal melanoma, a melanoma that appears in the vagina.

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