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I had the good fortune to work at the National Cancer Institute from 1965 to 2005. The National Cancer Institute provided an environment that permitted my curiosity to flourish. Colleagues, particularly Marston Linehan, were essential to performance of the work. The work described in this manuscript was performed during a period of rapid advances in genetics. I was able to apply my clinical training and new genetic tools to study human kidney cancer. With the support of the National Cancer Institute, I was able to canvas physicians throughout the United States and Canada for referrals of families with multiple members affected with renal cancer. I was able to visit these families in their communities and determine the clinical and genetic features of their hereditary susceptibility to renal cancer, and to bring these families to Bethesda for comprehensive examinations. Using DNA analytic tools, we were able to identify several tumor suppressor genes that play major roles in the pathogenesis of human renal carcinoma thus opening up new fields for biochemical research into the pathogenesis of human renal carcinoma.