Geographic variation in hepatocellular carcinoma (HCC) has not been previously studied in the United States. Using data collected by the Surveillance, Epidemiology, and End Results registries (SEER) and the 1990 Behavioral Risk Factor Surveillance System (BRFSS), we analyzed incidence and risk factors for HCC in nine geographic regions in the United States. We identified all individuals with HCC during 1975-1998 in five states (Connecticut, Iowa, Utah, New Mexico, and Hawaii) and four metropolitan areas (Detroit-Metropolitan, San Francisco-Oakland, Seattle-Puget Sound, and Atlanta-Metropolitan). Age-adjusted incidence rates were calculated for each geographic region. The association between HCC incidence and geographic regions were examined in Poisson multivariate regression model controlling for age, gender, race, and year of diagnosis. Hierarchical linear modeling was also used to examine these associations while adjusting for potential clustering of persons with similar characteristics within geographic regions, and to assess the effect of the prevalence of smoking, alcohol use, obesity, and diabetes in the underlying population in these geographical regions. A total of 11,547 persons with HCC were examined. Hawaii had the highest age-adjusted incidence rate (4.6), followed by San Francisco-Oakland (3.2), New Mexico (2.0), Detroit-Metropolitan (1.9), Seattle-Puget Sound (1.8), Atlanta-Metropolitan (1.7), Connecticut (1.6), Iowa (1.1), and Utah (1.0); all rates per 100,000. Whites had an age-adjusted incidence rate of 1.5, Blacks 3.2, and other races "Asian, American Indian, Pacific Islander" 7.0. However, Blacks and "other races" in Seattle-Puget Sound had higher age-adjusted incidence rates (4.4 and 8.2, respectively) than Blacks and other races in any other registry, while Whites in Hawaii had a higher rate (2.5) than Whites in any other registry. In general, men had a two to three times higher age-adjusted incidence rate than women. However, Hawaiian men had significantly higher age-adjusted rates (7.0) than men in other regions, while Utah had the lowest rates of HCC in men (1.5). Adjusting for variations in ethnicity, gender, age, and time of diagnosis, the Poisson regression analysis showed persistent geographic differences in HCC as well as a change in the order with New Mexico having the highest HCC incidence followed San Francisco-Oakland. Hierarchical linear modeling confirmed geographic variations in HCC but failed to show a significant effect for the prevalence of smoking, alcohol use, obesity, and diabetes in the underlying population. Significant geographic variation in HCC incidence exist in the United States. These variations are only partly explained by differences in age, gender, race, and year of diagnosis.