Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal, dominantly inherited syndrome which predisposes to the development of colorectal cancer and, to a lesser extent, other extracolonic neoplasms. Widespread microsatellite instability is a feature of nearly all tumors from patients with hereditary non-polyposis colorectal cancer. It was recently found that most patients under age 35 with colorectal cancer also have widespread microsatellite instability in their tumors and that many of these patients have the germline mutations of mismatch repair genes that characterize hereditary non-polyposis colorectal cancer. Renal cell carcinoma has occasionally been reported in patients with hereditary non-polyposis colorectal cancer, and some renal cell carcinomas have been shown to have microsatellite instability at multiple loci. For this reason, we sought to address the possibility that some young patients with renal cell carcinoma may have hereditary non-polyposis colorectal cancer by screening their tumors for microsatellite instability. Thirty-two patients under the age of 45 with renal cell carcinoma were examined for the presence of microsatellite instability in their tumor tissue. Microsatellite instability was not observed in any of the tumors. The absence of microsatellite instability in renal cell carcinomas from young patients suggests that these patients are unlikely to have hereditary non-polyposis colorectal cancer and would generally not benefit from genetic screening for this syndrome.