Background and objectives ESRD is associated with an increased risk of malignancies. We analyzed the incidence of cancer in patients with pediatric ESRD after long-term follow-up.Design, setting, participants, & measurements All Dutch patients born before 1979 who were transplanted at age ,15 years old in 1972-1992 were followed until 2010. We explored type and incidence of malignancies in patients compared with the general population using the National Cancer Registry.Results After a median of 25.3 years (1.3-37.8) of transplantation and at a median age of 33.5 years old (11.0-49.0), 105 primary malignancies had occurred in 54 of 249 patients. Among them, cutaneous squamous cell carcinoma was most frequent. Patients ages 25-30 years old had developed 16.5 times (95% confidence interval, 7.9 to 34.6) as many de novo tumors and 991 times (95% confidence interval, 313 to 3137) as many de novo cutaneous squamous cell carcinomas as their general population counterparts; in survivors ages 45-50 years old, these numbers were 81.5 (95% confidence interval, 50.7 to 131.1) and 2610 (95% confidence interval, 1596 to 4267), respectively. Cumulative incidence competing risk analysis showed that, after 30 years of transplantation, 41% of the survivors had developed cancer; 31% had developed a second de novo cancer ,1 year after initial cancer diagnosis.Conclusions Cancer is highly prevalent among patients with pediatric ESRD after 25.3 years of transplantation, with a high rate of recurrence.