Thyroid transcription factor (TTF-1) is a tissue-specific nuclear transcription factor expressed developing thyroid, respiratory epithelium, and diencephalon. TTF-1 is thought to be expressed specifically in most thyroid tumors and in a significant subset of pulmonary neoplasms. However, recent studies on its expression in extrapulmonary carcinomas have demonstrated that TTF-1 is not as specific for lung and thyroid carcinomas as was previously thought: positivity of this marker can be observed, although much less frequently, in some carcinomas arising in other organs, such as the ovaries, endometrium, colon, and breast, as well as in some tumors of the central nervous system. Case reports of patients with TTF-1-positive colon adenocarcinoma are present in medical literature, but there are only a few cases of TTF-1-positive rectal adenocarcinoma. We present the case of a patient with rectal adenocarcinoma with lung metastasis found to be TTF-1-positive on immunohistochemistry. A review of the available literature is also included.