OBJECTIVE To test the hypothesis that bladder cancer is a heterogeneous disease. PATIENTS AND METHODS We examined the temporal trends of bladder cancer by histological subtype and by disease stage and grade using the National Cancer Institute's Surveillance, Epidemiology, and End Results data collected in 1973-2007. RESULTS The age-adjusted incidence rates of bladder cancer showed a slight decrease from 1973 to 2007 (annual percentage change [ APC] = -0.4, P < 0.05). Although the age-adjusted incidence rates of non-papillary transitional cell carcinoma decreased by about 53% from 7.9 per 100 000 in 1973 to 3.7 per 100 000 in 2007 (APC = -2.2, P < 0.05), the ageadjusted incidence rates of papillary transitional cell carcinoma increased by about 56% from 6.8 per 100 000 in 1973 to 10.6 per 100 000 in 2007 (APC = 0.5, P < 0.05). Among other rare histological subtypes, except for small cell carcinoma which showed a slightly rising trend, squamous cell carcinoma, adenocarcinoma and others all presented a decreasing trend. Similar patterns were found for different stages (localized, regional and distant), but a dramatic increasing trend of grade IV was found between 1998 and 2007 when a corresponding decreasing trend was shown for grades I, II and III. CONCLUSION The results support the hypothesis that bladder cancer is a heterogeneous disease and taking disease heterogeneity into consideration in future epidemiological studies is essential.