The aim of this prospective study was to examine the prognostic pathomorphological factors in urothelial cancer of the urinary bladder. Clinical and morphological variables were evaluated by univariate and multivariate analysis in 70 patients with invasive transitional-cell carcinoma of the bladder (pTI-pT4a). The patients were treated according to a prospective program consisting of radical cystectomy and pelvic-node dissection, either alone or followed by adjuvant cisplatinum chemotherapy. Nodal status was pN0 in 89% of the patients. The median follow-up time was 5.75 years and the 5-year survival was 58%. Among the morphologic variables, deep invasion of the bladder wall and squamous differentiation indicated a poorer prognosis. Differentiation grade, pattern of growth (infiltrating versus expanding), angioinvasive growth, glandular differentiation and concomitant prostate carcinoma (pT1) were not significative factors for survival. By contrast, a significant reduction in mortality rate was found in patients with concomitant carcinoma in situ. Multivariate analysis confirmed that depth of invasion is an independent prognostic factor of outcome. The results confirm the primary importance of tumor stage in the prediction of survival after radical cystectomy. © Wiley-Liss, Inc.