In this study we have investigated amongst TKI erlotinib treated non-small cell lung cancer (NSCLC) patients the potential predictive outcome of three clinical practice applied serum biomarkers (CEA, CYFRA 21–1, SCC) together with the soluble form of EGFR (sEGFR) and its constituting ligands: epidermal growth factor (EGF), transforming growth factor-alpha (TGF-α) and heparin binding epidermal growth factor (HB-EGF). Here, HBEGF is linked to non-small cell lung carcinoma.