In this case, we report a patient with EGFR-mutated NSCLC who progressed on first-line osimertinib treatment, acquiring a nuclear receptor coactivator 4–rearranged during transfection (NCOA4–RET) fusion alongside a co-mutation in the tumor protein p53 (TP53) gene. This evidence concerns the gene TP53 and non-small cell lung carcinoma.