The expression of biomarkers by lung cancers is useful in the diagnosis and clinical management of patients with lung cancer. Biomarkers provide insight into histogenesis, interrelationships, and biological behavior of lung tumors. This chapter presents data on lung cancer detection, involving some of the most studied and interesting lung cancer biomarkers to date-CYFRA 21-1, NSE, ProGRP, SCC, CEA, Tumor M2-PK, as well as markers in clinical application such as CRP, LDH, tumor-suppressor genes and oncogenes, CA125, CgA, NCAM, and TPA. Biomarker profiles in combination with fuzzy logic techniques have also been addressed. Serum markers used alone or in combination with other indices might play an important role in monitoring response to therapy in early detection of tumor reactivation in new treatment strategies as well as in secondary prevention.