Thyroid transcription factor-1 (TTF-1) protein expression is widely used in the diagnosis of lung and thyroid carcinomas. Although there have been reports of TTF-1 immunoreactivity in tumors other than those originating in the lung or the thyroid, the expression of this marker has been studied in only a limited number of ovarian neoplasms. Our study examines the incidence of TTF-1 expression in a variety of ovarian epithelial neoplasms. Tissue microarrays of 138 ovarian serous carcinomas, 65 endometrioid adenocarcinomas, 35 mucinous adenocarcinomas, 30 mucinous neoplasms of low malignant potential, and 10 clear cell carcinomas were stained with anti-TTF1-antibody. In addition, whole tissue sections of 19 serous carcinomas, 5 endometrioid adenocarcinomas, 7 mucinous adenocarcinomas, and 3 clear cell carcinomas were stained. In the tissue microarrays, TTF-1 nuclear expression was demonstrated in 2 of 65 (3%) of the endometrioid adenocarcinomas; no nuclear immunoreactivity was identified in the remaining ovarian neoplasms. In the whole tissue sections, TTF-1 nuclear staining was present in 7 of 19 (37%) serous carcinomas, 1 of 5 (20%) endometrioid adenocarcinomas, and 1 of 3 (33%) clear cell carcinomas. In most of the positive cases, staining was focal, but in one endometrioid adenocarcinoma in the tissue microarray and in one serous and one clear cell carcinoma in the whole tissue sections, there was diffuse positivity. Overall, there was nuclear staining in 0.7% of tumors in the tissue microarray and 26% in the whole tissue sections. Although TTF-1 nuclear expression is generally considered to be a relatively specific marker for lung and thyroid neoplasms, the occasional immunoreactivity of ovarian carcinomas should be considered in the evaluation of neoplasms of unknown primary origin. It should also be taken into consideration when evaluating adenocarcinomas involving the lung in patients with a history of a gynecologic malignancy.