By performing molecular profiling at the Casa Sollievo della Sofferenza Hospital (San Giovanni Rotondo, Foggia, Apulia), our retrospective cohort study provides a unique real-world dataset to assess the frequency and distribution of mutations in lung cancer driver genes, such as EGFR and KRAS, in early-stage (stage I–IIIA) NSCLC patients from Southern Italy undergoing radical surgical resection. This evidence concerns the gene EGFR and non-small cell lung carcinoma.