Background: Primary small cell carcinoma of vagina (SCCV) is highly malignant and rare. Only 39 patients with this malignancy can be found in a search of the PubMed and MEDLINE database, and most of them died within 12 months of diagnosis. Cases: We report two patients with primary vaginal small cell carcinomas. Their tumors show similar histologic and ultrastructural neuroepithelial elements. Both of them underwent radical surgery, received different adjuvant therapy, and had different outcomes. One is without recurrence 36 months after surgery and the other recurred within 2 months of completing treatment. Conclusion: Although surgery for the treatment of early-stage disease is suggested, surgery followed by chemotherapy and radiation may be superior to surgery alone. Receiving chemotherapy and radiotherapy as soon as possible after surgery may improve patient prognosis.