The invention relates to methods for determining the clinical outcome of patients suffering lung cancer and being under treatment with an EGFR inhibitor. The methods are based on the detection of the presence of mutations in the EGFR gene conferring resistance to inhibitors of the EGFR tyrosine kinase activity, wherein the appearance of said mutations in the biofluid of the patient is indicative of a high probability that the patient suffers a relapse of the disease. The invention also provides therapeutic methods for said patients.