Early studies with tirosine kinase inhibitors (TKI), namely Erlotinib and Gefitinib, in patients with non small cell lung cancer (NSCLC), showed that although most patients did not respond radiologically, a small percentage of those patients (about 10%) had an excellent response to treatment, with radiological regression and clinical response duration. Four patient populations are known as having better response to TKI as opposed to other patients: adenocarcinoma patients, non-smokers, women and asians. Nevertheless, a good general status remains a predictive factor for treatment response. The discovery of the EGFR mutation in NSCLC patients' tumors and its association with clinical response to Erlotinib and Gefitinib, confirmed by a considerable number of retrospective and prospective studies, showed that response rates are between 75-80% in patients carrying this mutation. Although several mutations have been identified, the two commonest (approximately 90%) are located in exons 19 and 21. The authors present two patients studied and treated at the Pulmonology Department's Lung Oncology Unit of CHVNGaia, where Erlotinib was used as 3(rd) line treatment: in one patient, which was part of the population with good response to TKI, a classic exon 19 was identified, and was treated with Erlotinib for twenty months with clinical stability; the other patient did not belong to the above mentioned population and an Exon 20 mutation was identified (a mutation not yet described in literature, being not clear its association with response to treatment with TKI) - treatment was stopped after 7.4months due to disease progression. Rev Port Pneumol 2008; XIV (Supl 3): S43-S51.