Abstract: Objective To investigate thyroid transcription factor-1 (TTF-1) expression in normal human adult type Ⅱ alveolar epithelial cells, embryonic pneumocytes, lung carcinoma cells and lymph node metastases of lung cancer. Methods Lung carcinoma tissue microarray was constructed containing 765 cores of 20 normal adult lung tissues, 15 embryonic lung tissues, 100 lung carcinomas and 55 corresponding lymph node metastases. TTF-1 protein expression on the microarray was detected by immunohistochemical SP method using TTF-1 monoclonal antibody and assessed quantitatively with Leica Q500MC image analysis system. Results The number TTF-1 positive units (PU) was smaller in the nuclei of embryonic pneumocytes than in those of normal adult type Ⅱ alveolar epithelial cells (P<0.001). The nuclei of lung carcinoma cells had smaller TTF-1 PU than normal adult type Ⅱ alveolar epithelial cells and embryonic pneumocyte nuclei (P<0.001). The lung adenocarcinoma and small cell lung carcinoma cell nuclei had greater TTF-1 PU than squamous cell carcinoma and large cell lung carcinoma cell nuclei (P<0.001). TTF-1 PU was greater in squamous cell carcinoma cell nuclei than in large cell lung carcinoma cell nuclei (P<0.001). In lung adenocarcinoma, squamous cell lung carcinoma and large cell lung carcinoma, TTF-1 PU was greater in the cancerous cell nuclei of lymph node metastases than in the corresponding primary carcinoma cell nuclei (P<0.001, P<0.001, and P<0.05, respectively). In small cell lung carcinoma, TTF-1 PU of the cancerous cell nuclei of lymph node metastases was similar to that of primary carcinomas (P>0.05). TTF-1 PU was greater in lung carcinoma with lymph node metastases than in those withouts metastalsis (P<0.001). TTF-1 PU of the cell nuclei was not associated with the tumor growth pattern, differentiation and patients’ gender (P>0.05), but was greater in TNM stage Ⅱ-Ⅳ than in stage Ⅰ (P<0.001). Conclusions The amount of TTF-1 in the cell nuclei decreases in the order of normal adult type Ⅱ alveolar epithelial cells, embryonic pneumocytes and lung carcinoma cells. TTF-1 expression is higher in adenocarcinoma and small cell carcinoma and lower in squamous carcinoma and large cell carcinoma. Stronger TTF-1 expression is associated with greater likeliness of lung carcinoma metastatie, and can be an important hallmark for metastasis potential of lung adenocarcinoma, squamous cell carcinoma and large cell carcinoma.