Objective: Although proteomic profiles detected by using SELDI-TOF-MS method distinguish lung cancer patients from healthy individuals, there are no studies concerning proteomic patterns of tumor subsets in lung cancer. The goal of this study was to establish proteomic patterns of tumor subsets in lung cancer patients with surface enhanced laser desabsorbtion ionization time of flight mass spectrometry (SELDI-TOF-MS) method. Material and Methods: A total of 169 patients diagnosed histopathologically including 142 non-small cell lung cancer (NSCLC) and 27 small cell lung cancer (SCLC) patients were included in this study. In NSCLC group, there were 60 squamous cell carcinoma, 38 non-squamous cell carcinoma and 44 unclassified type NSCLC patients. Venous blood samples were obtained from all cases. All of the serum samples were analyzed by SELDI-TOF-MS method for proteomics investigation. Results: Three peaks (9065 m/z, 9175 m/z, 9394 m/z) were found to be discriminatory in serum SELDI profiles between NSCLC and SCLC groups (p<0.05). All of these three peaks showed higher intensity in patients with SCLC. The analysis between non-squamous and squamous cancer groups of NSCLC revealed eight discriminatory proteomic features. Among these peaks, only two (5815 m/z, 5906 m/z) showed higher intensity in patients in the non-squamous group (p<0.05). Conclusion: Proteomic patterns could provide some valuable clues on the carcinogenetic mechanism of different types of lung cancer and may help us to discover some potential subtype-specific biomarkers of lung cancer by SELDI-TOF-MS method. © 2012 by Türkiye Klinikleri.