Peroxisome Proliferator Activated Receptor-gamma (PPAR-gamma) is a ligand-activated transcription factor belonging to the steroid receptor superfamily. It is a key regulator of adipogenic differentiation and glucose homeostasis, the ligands of which have also been demonstrated to induce differentiation in human breast, lung and colon cancer cell lines. In the present study, PPAR-gamma expression in cases of non-small cell lung carcinoma (NSCLC) was examined immunohistochemically and was correlated with tumor histological type and grade. Primary tumor samples from 147 patients with NSCLC were immunostained using a monoclonal antibody against PPAR-gamma. Positive PPAR-gamma immunostaining was prominent in 61 out of 147 cases (42%) and negative in the rest. PPAR-gamma positivity was prominent in 37 out of 79 cases (47%) of squamous cell lung carcinoma and in 24 out of 68 ones (35%) of lung adenocarcinoma. PPAR-gamma positivity was most frequently observed in squamous cell tumors (P=0.021) and in tumors of high histological grade of both histological types (P=0.041). Well-differentiated adenocarcinoma cases presented increased frequency for PPAR-gamma positivity compared with moderately and poorly differentiated ones (P=0.001). The intensity and pattern of PPAR-gamma staining in tumor cells were not correlated with histopathological parameters in PPAR-gamma positive cases of NSCLC examined. Our findings support evidence for participation of this protein in the biological mechanisms underlying the carcinogenic evolution in the lung, suggesting also the importance of specific PPAR-gamma ligands as future therapeutic approach in lung cancer.