In conclusion, despite the small number of patients involved, the retrospective analysis and the low rate of re-biopsies, our results confirm the importance of cftDNA analysis for the monitoring of secondary mutations associated with EGFR-TKI resistance in NSCLC and underline the role of a highly sensitive approach, i.e., ddPCR, for the detection of low-level mutations. The gene discussed is EGFR; the disease is non-small cell lung carcinoma.