Non-small cell lung carcinomas (NSCLCs) commonly present as 2 or more separate tumors. They encompass separate primary lung carcinomas (SPLCs), representing independently arising tumors, or intrapulmonary metastases (IPMs), representing intrapulmonary spread of a single tumor. In this episode, Dr. Natasha Rekhtman, from Memorial Sloan Kettering Cancer Ctr, NY provides an update on the growing applications of genomic testing as a clinically relevant benchmark for determining clonal relationships in multiple NSCLCs. She discusses the limitations of morphology-based distinction of SPLCs vs IPMs and the pivotal insights that have emerged from studying multiple NSCLCs using genomic approaches as a gold standard.