OBJECTIVE This study aimed to examine the clinicopathological characteristics, treatment, and prognostic factors in 12 cases of malignant transformation of mature cystic teratoma of the ovary (MCTO). METHODS We performed a retrospective study of 12 patients with malignant transformation of MCTO who were admitted to the Affiliated Hospital of Qingdao University from 2003 to 2019. We examined case records, clinical parameters, and biological assessments. RESULTS The median age of the patients was 56.5 years and seven of them were postmenopausal. The average tumor size was 18.5 cm. All patients had pelvic masses at their first hospital visit. Nine of the patients had discomfort in the lower abdomen, two presented with a lower abdominal palpable mass, and three were complicated by fever. The median follow-up time was 73 months (12‒193 months). Ten patients survived with a disease-free status and two died. CONCLUSIONS There is a low incidence of malignant transformation of MCTO, and its most common histological type is squamous cell carcinoma. Age and tumor size are important factors in malignant transformation of teratomas. While there is a lack of treatment guidelines for malignant transformation of MCTO, early diagnosis and treatment may be beneficial for these patients.