An empirical evaluation of long-term period survival analysis was performed using data from the Childhood Cancer Registry of Piedmont, Italy. The aim was to update survival time trends and provide 25-year projections for children currently diagnosed with cancer. The observed survival experiences up to 15 years after diagnosis of five quinquennial cohorts (cohort analysis) were compared to the corresponding estimates obtained by period analysis. The two methods generally produced very similar findings, although period analysis estimates were slightly lower than those obtained from cohort analysis. We then used mixed analysis to assess time trends in long-term survival. This showed that the probability of surviving 25 years after a cancer in childhood has more than doubled compared to cohort analysis estimates from patients diagnosed more than 25 years ago (73% vs. 32%), providing further evidence of an ongoing improvement in prognosis.