The Erb-B family of receptors plays an important role in lung carcinogenesis and tumor development, and EGFR and HER2 are highly expressed in bronchial preneoplasia. In invasive tumors, EGFR are expressed in 50-90%, and mostly in squamous cell carcinomas, but also in adenocarcinomas and large cell carcinomas, while HER2 is less frequently expressed (20-30%) and mostly expressed in adenocarcinomas. Bronchioloalveolar cell carcinomas may present a distinct EGFR profile compared to the other NSCLCs and evidence and consequences are discussed. The genetic mechanisms responsible for overexpression of EGFR and HER2 proteins might be numerous, including gene dosage (overrepresentation or amplification) as well as translational and post-translational mechanisms. However, for EGFR and HER2 there is a positive correlation between gene copy numbers and level of protein expression demonstrated by fluorescence in situ hybridization analysis and immunochemistry. Gene amplification for EGFR and HER2 is demonstrated in only 5-10% of the tumors. The treatment status and therapeutic limitation with trastuzumab (Herceptin) in lung cancer compared to breast cancer is discussed.