A cohort of 233 T2/T3 transitional cell carcinomas were followed up for over 10 years. Five nuclear factors, two mitotic indices, DNA ploidy and S-phase fraction (SPF) were related to progression and survival of TCCs during that time period. SPF predicted pelvic lymph node involvement at diagnosis (P = 0.064). Progression in T-category was related to T-category (P = 0.035), DNA ploidy (P = 0.0180), papillary status (P = 0.0021), mitotic activity index (MAI) (P = 0.0011), volume corrected mitotic index (M/V index) (P = 0.0017), WHO grade (P = 0.0003) and S-phase fraction (P = 0.0002). Progression in N and M-categories was related to the same variables. Independent predictors of progression in T-category were SPF (P = 0.0161) and WHO grade (P = 0.0236), whereas progression in M-category was independently related to MAI (P = 0.0012) and T-category (P = 0.0004). The SPF (P < 0.0001), M/V index (P < 0.0001), MAI (P < 0.0001), WHO grade (P < 0.0001) and papillary status (P < 0.0001) were the most important predictors of survival in univariate analysis. In a multivariate analysis SPF and M/V index (P < 0.0001) were the best predictors of survival followed by papillary status and T-category. The results show that the proliferation rate of T2/T3 TCCs as determined by flow cytometric SPF or M/V index are equally powerful predictors. They are clearly better than nuclear morphometry, DNA ploidy or WHO grading as prognostic factors.