Objective: Deregulation of the PI3 kinase-AKT/mTOR pathway is a frequent event in tumorigenesis. We examined the possible significance of the components of this pathway in bladder urothelial carcinoma (UC). Method: 108 cases with bladder UC were screened for mutations in exons 9, 20 of PIK3CA gene and exon 4 of AKT1 by PCR-SSCP, HRMA, sequencing and/or Pyrosequencing. The expression of p-mTOR, p-4E-BP1, p-p70S6K, p-AKT, FGFR3 and p-ERK was evaluated by immunohistochemistry. Results: 4,6 % of the cases were mutant in PIK3CA gene and 3 % in AKT1. Cases with wild type AKT1 displayed higher FGFR3 receptor expression (p=0.0521). p-4E-BP1 expression was more frequent in low grade (p=0.018) and in pTa-T1 tumors (p = 0.053). Furthermore, superficial tumors presented higher levels of p-p70S6K expression (p = 0.035) and lower levels of p-AKT expression (p = 0.048). In multivariate survival analysis, p-4E-BP1 immunoexpression emerged as an independent prognostic factor of adverse survival (HR =9.207, p=0.0039), along with tumor grade and T-category. Conclusion: Activation of PI3K/AKT/mTOR pathway in bladder UC is not exclusively related to the presence of AKT1 and PIK3CA mutations. Expression of p-4E-BP1 could serve as an independent prognosticator.