TTF1 (Thyroid Transcription Factor 1), also known as NKX2-1. is a transcription factor encoded by the NKX2-1 gene located on chromosome 2p13. It belongs to the NKX2 family of homeodomain-containing proteins and plays a critical role in embryonic development, particularly in the morphogenesis and differentiation of the thyroid, lung, and specific regions of the brain. In diagnostic pathology, TTF1 is widely utilized as an immunohistochemical (IHC) marker to determine the origin of tumors. It is highly expressed in adenocarcinomas of the lung (specifically terminal respiratory unit-type) and thyroid neoplasms (e.g., papillary and follicular carcinomas). TTF1 positivity helps distinguish primary lung adenocarcinomas from squamous cell carcinomas (usually TTF1-negative) and metastatic tumors from other sites. Additionally, it is expressed in a subset of neuroendocrine tumors, including small cell lung carcinoma. However, TTF1 expression can vary depending on tumor type, differentiation status, and antibody clones used (e.g., SPT24 vs. 8G7G3/1 clones). Its specificity and sensitivity make it a cornerstone in tumor classification, though results should always be interpreted alongside clinical, radiographic, and histologic findings.