In this study, we have found that a common phenotype, which is correlated to acquired resistance following long term in vitro treatment with four different TKIs, such as two EGFR inhibitors (erlotinib and gefitinib) and two broad spectrum kinase inhibitors (vandetanib and sorafenib), of human CALU-3 lung adenocarcinoma cells, is represented by the acquisition of EMT cellular properties with the combined loss of epithelial cell junction proteins, such as E-cadherin, and the gain of mesenchymal markers, such as vimentin. Here, EGFR is linked to lung adenocarcinoma.