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OBJECTIVE: This study describes current childhood cancer incidence in the United States and identifies demographic and geographic variation among children and adolescents with cancer.METHODS: We examined data from 39 National Program of Cancer Registries and 5 Surveillance, Epidemiology, and End Results statewide registries (representing over 90% of United States population) to identify cancers diagnosed among persons aged 0-19 from 2001 and 2003.Diagnosed cancers were grouped by the third version of International Childhood Cancer Classification.Analyses were stratified by sex, age, race, ethnicity, and U.S.Census region.A multivariable negative binomial regression model was used to evaluate demographic and geographic differences in incidence for all cancers combined.RESULTS: We identified 36446 cases of childhood cancer with an age-adjusted incidence rate of 165.92 per million.Stratified analyses showed that, for all cancers combined, boys had a significantly higher rate than girls (RR, 1.11; 95% CI, 1.09-1.13); children (0-14 years) had a significantly lower rate than adolescents (15-19 years) (RR, 0.72; 95% CI, 0.70-0.73); whites had the highest incidence rate among all races (P<0.05).Young people living in the Northeast had the highest incidence rate among all U.S.Census regions (P<0.05), which may be partially attributed to significantly higher incidence rates for central nervous system (CNS) neoplasms and lymphomas in this region compared to other U.S.Census regions (P<0.05).The negative binomial regression analysis demonstrated that childhood cancer incidence rate varied significantly by sex, age, race, ethnicity, and geography (all P<0.05).CONCLUSIONS: This study is the first to demonstrate substantial regional differences in the incidence of childhood cancer.It also shows that incidence varies by sex, age, race and ethnicity.Our research fmdings are useful to prioritize future childhood cancer research needs.