Investigation of the genomic instability of microsatellite repeats indicates a new mechanism for human carcinogenesis. This study was conducted to determine whether such alterations in microsatellite repeats are associated with the onset of bladder cancer. Thirty-two primary bladder cancer DNA samples were examined for genomic instability at (CA)n repeats on human chromosomes 5q (D5S107), 17p (D17S261) and 18q (DCC) by polymerase chain reaction (PCR) assay. Differences in unrelated microsatellites for tumor and normal DNA were detected in 6 of the 32 (18.8%) tumors examined. These six tumors were beyond grade 2 and stage pT2 invasive bladder tumors. However, only one of 32 (3.1%) showed alterations with more than 2 microsatellite probes. It follows that alterations of (CA)n microsatellite instability may be infrequent in the tumorigenesis of bladder cancer.