BACKGROUND The pattern of cancer in long-term survivors from childhood cancer has not been investigated comprehensively. METHODS We obtained a cohort of 47,697 children and adolescents aged 0-19 years with cancer as defined by the country-wide cancer registries of Denmark, Finland, Iceland, Norway, and Sweden during 1943-2005. Cohort members were followed through age 79 years for subsequent primary cancers notified to the registries, and the age-specific risk pattern of the survivors was compared with that of the national populations using country and sex standardized incidence ratios (SIRs). We used a multiplicative Poisson regression model to estimate relative risk of cancer for attained age, with adjustment for calendar period and age at diagnosis of primary cancer. We also calculated excess absolute risk (EAR) attributable to status as childhood cancer survivor and determined the cumulative incidence of second primary cancer as a function of attained age for three subcohorts defined by period of treatment for childhood cancer. RESULTS A total of 1180 asynchronous second primary cancers were observed in 1088 persons, yielding an overall SIR of 3.3 (95% confidence interval = 3.1 to 3.5). The relative risk was statistically significantly increased in all age groups, even for cohort members approaching 70 years of age. The EAR for second primary cancer among survivors increased gradually from one additional case per 1000 person-years of observation in early life to six additional cases per 1000 person-years in the age group 60-69 years. For children treated in the prechemotherapy era (1943-1959), the cumulative risk for a second primary cancer reached 18%, 34%, and 48% at ages 60, 70, and 80 years, respectively. The age-specific incidence rates were highest for cohort members treated in the era of intensive, multiple-agent chemotherapy (1975-2005). CONCLUSION Survivors of childhood cancer have a persistent excess risk for a second primary cancer throughout their lives, accompanied by continuous changes in the risk of cancers at specific sites.