Recent studies described the existence of genetic instability associated with bladder carcinogenesis. Alterations at microsatellite loci constitute a recognized tumor marker of genome instability. A series of 21 transitional cell carcinomas of the bladder (10 superficial and 11 invasive carcinomas) was analyzed for the presence of alteration in 12 microsatellite loci, in order to detect the role of microsatellite instability in genesis and progression of human bladder cancer. Our preliminary results indicate a trend to presence of microsatellite instability (MI) in invasive and undifferentiated tumors compared to superficial and differentiated forms. Eight out of 11 T2-T4 tumors presented a number of altered microsatellite >/=2 compared to one out of 10 Ta-T1 bladder carcinomas (p=0.008). Moreover, 9 out of 15 (60%) G2-G3 tumors had significantly more unstable microsatellites than those differentiated (0 out of 6) (p=0.019). Our results provide an insight into the potential usefulness of microsatellite analysis of bladder carcinoma to better understand which neoplastic forms will evolve to invasive progression and indicate that pronounced MI may be associated with more aggressive bladder carcinomas.