From this large real-world cohort of patients with RET fusion-positive, advanced or metastatic NSCLC, we report the following: (1) high antitumor activity of pralsetinib delivered in the late line setting; (2) the aggressiveness of disease progression on pralsetinib; and (3) the poor understanding of resistance mechanisms given infrequent rebiopsy and genomic profiling at progression. This evidence concerns the gene RET and non-small cell lung carcinoma.