William Y. Kim, MD, a renowned expert from the University of North Carolina, joins JAMA Associate Editor David L. Simel, MD, MHS, to dive deep into renal cell carcinoma. They discuss groundbreaking links to Nobel-winning research on tumor suppressors and hypoxia-inducible factors. The conversation covers diagnostic challenges, genetic screening, and the importance of evaluating familial history. Treatment options are also highlighted, emphasizing advancements in surgical techniques and personalized therapies for advanced stages of the disease.