This paper examines whether carcinogenic pollutants discharged from US Toxics Release Inventory (TRI) facilities are related to cancer hospitalization rates among the general population in rural and urban areas. We analyzed cancer hospitalizations (N = 440,061) across 20 states to find age- and sex-adjusted population cancer hospitalization rates. Multiple regression models were used to determine whether cancer hospitalization rates at the county level (N = 1102 counties) were associated with higher levels of carcinogenic discharges from TRI facilities, controlling for other risks. Significantly higher hospitalization rates were found in relation to higher TRI discharges for several cancer types that varied from urban to rural setting. Carcinogenic discharges from TRI facilities were associated with excess inpatient cancer treatment costs of $902.8 million in 2009. Future research may strive to move beyond ecological designs to examine cancer risks from TRI releases to better our understanding of cancer etiology and to establish appropriate environmental safeguards as indicated by the evidence.