Purpose: Because we have found that random mucosal biopsies have no additional prognostic value to conventional histopathology, we studied biopsies of histologically normal bladder mucosa with several molecular markers believed to be associated with the development of transitional cell carcinoma. Materials and Methods: Six groups of patients with an increasing stage of bladder tumor were selected: (1) benign disease (for example, benign prostatic hyperplasia, n = 8); (2-4) low (n = 10), intermediate (n = 9) and high risk (n = 7) superficial tumors; (5) progressive superficial tumors resistant to optimal conservative therapy (n = 6); (6) invasive or disseminated tumors at presentation (n = 5). We studied the expression of cytokeratin (used as an epithelial marker), fibronectin, E-cadherin (HECD-1), I-CAM, human leukocyte antigen (HLA)-I, HLA-II and epidermal growth factor receptor (EGF-R) in cold-cup biopsies of normal mucosa. Results: Fibronectin, HECD-1, I-CAM and HLA-II expression showed no significant changes in the different groups. There was a significant increase in the expression of HLA-I (p = .003) and EGF-R (p = .0001) with a higher stage of the tumor. Conclusion: An increasing EGF-R expression in normal looking mucosa of patients with increasing stages of bladder tumors could be a prognostic factor or might indicate that this increase in expression is not tumor specific but is seen in the whole bladder.