The management of advanced lung cancer has changed in recent years, young and long-surviving patients with chronic diseases and good clinical conditions are frequently observed. These patients need complex, integrated and personalized treatments. The possibility of obtaining more information about the genomic profile would allow the identification of patients who could benefit from chemotherapy rather than immunotherapy or molecular target therapies. Below is the case of a 44-year-old man, ECOG PS 0, with stage IV lung cancer. This clinical history confirms the importance of a personalized approach. The patient, with non-oncogene addicted lung adenocarcinoma, achieves a good clinical-instrumental response after a first line of treatment, followed by a long maintenance phase for a total of 52 weeks. Upon progression, the patient maintains excellent clinical conditions over time, and three additional lines of therapy are carried out. At the end of this sequence, we have proposed a genomic profiling test on a tissue sample of the disease (next generation sequencing - NGS). The study, which also included the state of microsatellites and tumour mutational burden, identified the genetic alteration ATM - Q2762fs*6 (ataxia telangiectasia mutated, ATM) and for this reason we have administered niraparib for off-label use. Although this is not a standard clinical practice context, the case presented can be considered an example of a future strategy in which the ab initio identification of the rare genetic alteration, driver for tumour disease, could represent the first step in the diagnostic-therapeutic process. By improving knowledge on genetic alterations and identifying the most influential alterations for each single solid tumour, it will be possible to identify the most effective therapy, probably with even lower costs in terms of overall patient management.