Malignant transformation in a mature cystic teratoma of the ovary is rare. The most common malignancy is squamous cell carcinoma, which consists of about 75% of malignant transformations. In the present report, we describe a case of advanced-stage squamous cell carcinoma arising in a mature cystic teratoma. A postmenopausal 63-year-old woman with squamous cell carcinoma arising in a mature cystic teratoma is presented. The initial investigation by ultrasound showed a left adnexal mass with mixed echo pattern, which arose the suspension of malignancy. She underwent a laparotomy and left oophorectomy. Histopatholog was compatible with squamous cell carcinoma arising in a mature cystic teratoma. After a few episodes of intestinal obstruction and colostomy, she underwent partial resection of the ileum and sigmoid colon four months after the initial oophorectomy. Histopathologic study showed metastatic poorly-differentiated squamous cell carcinoma. Subsequently, she underwent two courses of combination chemotherapy with cisplatin, leucovorin, and 5-fluorouracil with no response. She died from progression of the disease nine months after the initial operation.