If a patient's cancer progresses while undergoing targeted therapy, a re-biopsy is not mandatory. But when evaluating the benefits and risks on a case-by-case basis (transformation to small cell, assessing for a clinical trial), physicians should inform patients about the possible need for a re-biopsy (5). This was a retrospective and multicentre study. A total of 644 patients with lung adenocarcinoma were reviewed, 625 of whom were ruled eligible. From them, 399 were found to show disease progression, and 126 re-biopsies were performed. Progression status, re-biopsy sites, success of obtaining adequate tissue, molecular patterns after re-biopsy and subsequent treatments were analysed. Survival differences among patients with disease progression were then examined according to re-biopsy status. Overall, 625 patients with adenocarcinoma and a median age of 61.4 were evaluated. Initial tyrosine kinase inhibitor (TKI) usage numbered 37 patients (5.9%). Progression was diagnosed in 399 (63.8%) patients, out of which 26 (31.6%) underwent re-biopsies. The successful number of re-biopsies was 103 (81.7%). No complications were observed after any of the biopsy procedures. Subsequent treatments were changed in 15 patients (11.9%), who began new TKI treatments. Poor performance status was the most common reason for not performing a biopsy (n = 65; 23.8%), followed by the physician's decision (n = 40; 14.6%). Re-biopsies can demonstrate the new characteristics of a tumour and can detect the activation of pre-existing clones, making possible new treatment opportunities for patients. According to the performance status of the patient and the availability of the progressive lesion, we should increase the rate of re-biopsies before the decision to follow up with the best supportive care.