The evaluation of individuals with lung cancer for the presence of oncogenic mutations and the subsequent administration of personalized targeted therapies are of significance in clinical practice. Epidermal growth factor receptor (EGFR) mutation and mesenchymal-epithelial transition (MET) exon 14 skipping mutation were previously found to be mutually exclusive. The co-occurrence of these mutations in individuals diagnosed with adenocarcinomas signifies a distinctive and uncommon molecular subtype of non-small cell lung cancer. A 70-year-old man was admitted to Shandong Cancer Hospital and Institute (Jinan, Chian) with a 1-month history of chest pain. The CT scanning findings indicated the presence of a 5.8×5.6 cm mass in the left lower lobe, accompanied by enlarged mediastinal and hilar lymph nodes, as well as metastases in both lungs and bones. Analysis of a biopsy specimen showed lung adenocarcinoma. Gene examination revealed EGFR Del19 mutation and concomitant MET exon 14 skipping mutation. Osimertinib and Gumarontinib were administered for 8 months and the efficacy was determined to be a partial response. The present study marks the initial discovery of MET exon 14 skipping and EGFR Del19 in a single patient, who achieved partial response through a treatment plan involving Osimertinib and Gumarontinib. These findings provide valuable perspectives on treatment approaches for individuals sharing similar genetic profiles.Copyright: © 2025 Jing et al.