Objective: Somatic alterations of K-RAS, EGFR and ALK which are increasingly requested in order to predict response to personalized therapies in lung cancer are mutually exclusive and are represented in over 50 % of lung adenocarcinomas. The approach to be followed for planning analyses is not standardized in the literature. Method: We have studied by molecular methods (PCR-RFLP for K-RAS, direct sequencing for EGFR and FISH for ALK) 185 formalin fixed, paraffin embedded cases of lung adenocarcinomas of different subtypes. Results: Based on rational, biological and economic considerations we started with K-RAS analysis by PCR-RFLP, which showed mutations in 38 cases (37 with mutation on codon 12 and one case with mutation on codon 13), The 147 residual cases were all analyzed for EGFR mutations. FISH for ALK translocation followed in EGFR-wild cases. Conclusion: The analysis for K-RAS mutations allows to select the significant percentage (approximately 25 % of adenocarcinomas) when EGFR mutation analysis by direct sequencing can be postponed. K-RAS and EGFR wild cases will then undergo FISH analysis for ALK translocation. ACKNOWLEDGEMENTS Study conducted with the support of the following project: Project PERSOTHER -SMIS-CSNR: 549/12.024; With the support of Sectoral Operational Programme "INCREASE OF ECONOMIC COMPETI-TIVENESS" Priority Axis 2: Research, Technological Development and Innovation for Competitiveness.