Thyroid transcription factor-1 (TTF-1) 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 thyroid, endocervical and endometrial adenocarcinomas have not been studied in large numbers. Our study provides data regarding the incidence and distribution of TTF-1 expression in these tumors. Twenty-eight endocervical (9 well, 12 moderately, and 7 poorly differentiated), 32 endometrioid endometrial adenocarcinomas (11 grade I, 8 grade II, and 13 grade III), and 13 uterine serous carcinomas were retrieved and stained with TTF-1. None of the tumors had a neuroendocrine component. The hematoxylin and eosin and anti-TTF-1 antibody stained sections were reviewed, and the presence and distribution of TTF-1 nuclear positivity was recorded. A semiquantitative grading system used to evaluate the distribution of TTF-1 staining (0 = negative, 1+ = <5%, 2+ = 5% to 25%, 3+ = 26% to 50%, 4+ = 51% to 75%, and 5+ = >75%). TTF-1 expression was seen in 1 of 28 (4%) of the endocervical adenocarcinomas and this was 4+ in distribution. The positive endocervical carcinoma was poorly differentiated. TTF-1 expression was present in 6 of 32 (19%) of the endometrioid adenocarcinomas (1 grade I, 2 grade II, and 3 grade III) and varied from 1+ to 4+ in distribution. Only 2 of 32 (6%) of the endometrioid adenocarcinomas stained diffusely (4+). There was no apparent correlation between the degree of differentiation and TTF-1 positivity in the adenocarcinomas. Three of 13 (23%) serous carcinomas were also positive (1 case 5+ and 2 cases 1+). Although TTF-1 is generally considered to be a relatively specific marker for lung and thyroid neoplasms, the occasional expression of endometrial and endocervical carcinomas should be kept in mind when evaluating neoplasms of uncertain origin. It should also be taken into consideration in the evaluation of adenocarcinomas involving the lung in patients with a history of a gynecologic malignancy.