A 65-year-old woman with a history of recurrent vaginal intraepithelial neoplasia was found to have small cell carcinoma (SCC). Exfoliative cytology was instrumental in the discovery of each episode of vaginal neoplasia. Thorough examination of the patient established the tumor as being primary to the vagina, and immunohistochemistry confirmed it to be a neuroendocrine SCC. Eleven patients with neuroendocrine SCC of the vagina have been reported previously. Morphologic characteristics and histogenesis are discussed within the context of the embryology and natural history of extrapulmonary-genital SCC. They have been classified in the amine precursor uptake and decarboxylation family of neoplasms. Originally, a neuroectodermal origin was proposed, but derivation now is thought to be from multipotential epithelial stem cells of the genital tract. Neuroendocrine SCC tends to be an aggressive neoplasm with a propensity for early spread. Long-term survival for patients with vaginal SCC has not been documented. Therapeutic decisions regarding SCC from this site have been based on information gained from the treatment of these tumors elsewhere. Combined modality therapy using initial surgery and adjuvant treatment, including systemic chemotherapy and local exposure to radiation, has produced an apparent complete response in our patient.