Tthyroid transcription factor 1 is a marker of lung and thyroid carcinomas, but thyroid transcription factor 1 immunoreactivity is seen in other malignancies. We examined the incidence of thyroid transcription factor 1 expression in gynecologic tumors in Japanese patients, and we further evaluated the presence of epidermal growth factor receptor mutations in thyroid transcription factor 1-positive gynecologic malignancies. A total of 186 patient samples collected at our hospitals between 1991 and 2006 were analyzed, and these specimens consisted of 83 ovarian carcinomas, 55 endometrioid endometrial adenocarcinomas of the uterus, 28 cervical adenocarcinomas of the uterus, and 20 leiomyosarcomas of the uterus. Thyroid transcription factor 1 expression was assessed by immunohistochemistry. The presence of epidermal growth factor receptor mutations was investigated by polymerase chain reaction analyses. Thyroid transcription factor 1 was detected in the nuclei of 11 ovarian carcinomas (13%) and 5 endometrioid adenocarcinomas (10%) of the uterus. In patients with ovarian carcinoma, thyroid transcription factor 1 staining was associated with significantly improved progression-free (P = .017) and overall survival (P = .017) using univariate analysis. Multivariate analysis identified thyroid transcription factor 1 expression as an independent prognostic factor for ovarian cancer (P = .0467). No epidermal growth factor receptor mutations were found in our study. Thyroid transcription factor 1 is expressed with relatively low frequencies in gynecologic malignancies, but thyroid transcription factor 1 expression confers a better prognosis in patients with ovarian cancer. No epidermal growth factor receptor mutations were found in the thyroid transcription factor 1-positive gynecologic malignancies, and we were unable to establish a relationship between epidermal growth factor receptor mutations and thyroid transcription factor 1 immunopositivity, as was previously shown for lung cancer.