Multiple primary malignancies in an individual patient are thought to be a common feature of hereditary disease. Asymptomatic renal neoplasms have been described in up to 4% of rectal cancer patients. We have assessed whether microsatellite instability is present in the rectal and renal tumors of patients presenting at our institution with primary renal and rectal cancers. Of the seven patients presenting with both diagnoses, paraffin blocks were available from five cases of colorectal cancer and six renal neoplasms. Five of six cases of renal tumors were informative and all were microsatellite instability (MSI) stable. One renal tumor was deemed inconclusive because of inadequate amplification. Four of five cases of rectal cancer were MSI stable. These data suggest that these renal and rectal tumors developed independently of a mismatch repair defect and that, unlike epithelial tumors of the renal collecting system, renal parenchymal lesions are unlikely to be part of the spectrum of hereditary nonpolyposis colorectal cancer.