Treatment results of 26 patients with squamous cell carcinoma (SCC) arising in mature cystic teratoma of the ovary were analyzed. Four nulliparous patients with stage Ia tumors underwent conservative salpingo-oophorectomy. Following surgery, 2 patients had successful pregnancies. The remaining 7 patients with stage Ia tumors were observed after hysterectomy and bilateral salpingo-oophorectomy. Fifteen patients with stage Ic-IV tumors underwent cytoreductive surgery followed by cis-platinum-based chemotherapy with or without sequential radiotherapy. The mean survival was 63.9 months. The overall actuarial disease-free survival at 2 years was 69%, and by stage was as follows: stage I, 100% (13/13); stage II, 100% (2/2); stage III, 30% (3/10); and stage IV, 0% (0/1). A significant difference in disease-free survival was noted in stage (P = 0.0001). Optimal versus suboptimal operation was associated with a median Kaplan-Meier survival of 65 months versus 34.8 months, with actuarial disease-free survival at 2 years of 60 and 0%, respectively (P = 0.0210). Our study shows that 67% (16/24) of the patients had SCC antigen levels exceeding 2 ng/ml, which by stage was as follows: stage I, 5/11 (45%); stage II, 1/2 (50%); stage III, 9/10 (90%); and stage IV, 1/1(100%). After completion of treatment, all 8 patients with recurrent lesions had reelevated SCC antigen levels in series SCC antigen monitoring. In conclusion, positive prognostic factors of disease-free survival were optimal cytoreduction and lower FIGO stage. We suggest that multimodality therapy, including aggressive cytoreduction followed by cis-platinum-based chemotherapy with or without sequential radiotherapy, is recommended. In addition, we suggest that serum SCC antigen monitoring may be helpful in early detection of cancer recurrence.