We studied the expression and mutation of thyroid transcription factor-1 (TTF-1) gene in 92 cases of lung carcinomas comprised of lung adenocarcinoma (36 cases), squamous cell lung carcinoma (42 cases), small cell lung carcinoma (8 cases), and large cell lung carcinoma (6 cases) to investigate whether TTF-1 gene mutation predisposed to the development of lung cancer. Normal lung tissues were obtained from each of the 92 patients. The tissues served as controls. Polymerase chain reaction–single-strand conformation polymorphism, denaturing high-performance liquid chromatography, and DNA sequencing were used to analyze TTF-1 gene mutation and its relationship with the carcinogenesis of lung cancer. We detected the expression of TTF-1 protein and messenger RNA (mRNA) in paraffin-embedded lung carcinomas and their normal lung tissues by tissue microarray. TTF-1 protein and mRNA intensities were measured by Leica-Q500 MC Image Analysis System to reveal their correlation with TTF-1 mutation in lung carcinomas. TTF-1 gene missense and synonymous mutation are present in lung carcinomas with the mutation rate of 16%. TTF-1 protein and mRNA are higher in normal lung tissues than in different lung carcinomas. TTF-1 gene mutation is correlated with the loss of TTF-1 protein and mRNA. The analyses of TTF-1 gene missense mutation and synonymous mutation and the loss of TTF-1 protein and mRNA can be regarded as the important indexes of molecular pathology of lung carcinoma.