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Malignant transformation of mature cystic teratomas is rare. The relatively low incidence of this event precludes large randomized studies, which may elucidate effective treatment modalities. We present a case of locally advanced disease (stage IIC) of squamous cell carcinoma of the ovary that arose within a mature cystic teratoma. By using multimodality treatment, including surgical resection, 3 cycles of chemotherapy, extended pelvic radiation followed by an additional 3 cycles of chemotherapy, we have achieved a 5-year disease-free interval. By publishing these data, we hope to add to the current body of literature as well as to aid in the treatment of this rare entity.