Activating mutations of fibroblast growth factor receptor 3 (FGFR3), found in autosomal dominant human skeletal dysplasia, were reported to be involved in tumorigenesis and correlate with low-grade and superficial lesions of urothelial carcinoma. FGFR3 protein expression was immunohistochemically investigated in 126 cases of urothelial carcinoma of the urinary bladder to evaluate the role of this receptor in tumor behavior. p53 expression and the proliferating activity of tumor cells, assessed by Ki-67 expression, were also analyzed in parallel. Cytoplasmic and/or membrane immunostaining for FGFR3 was observed in 62 (49.2%) cases, including 20 (15.9%) cases of intense staining and 42 (33.3%) of moderate staining. p53 expression and Ki-67 labeling index (LI) were significantly correlated with high tumor grade (p=0.0093 and <0.0001, respectively) and invasion (p=0.0041 and <0.0001, respectively). Although there were two groups of interesting cases: low-grade and non-invasive tumors negative for p53 but positive for FGFR3, and high-grade and invasive tumors positive for p53 but negative for FGFR3, no statistically significant relationship was found between FGFR3 expression and tumor grade, invasion, p53 expression or Ki-67 LI. These results suggest that FGFR3 protein expression in bladder cancer is unlikely to affect tumor behavior as a unique single factor.