Introduction The development of cancer programs in developing countries to meet the standards observed in high‐income developed countries is not well documented. Methods An analysis of patient care of children with acute lymphoblastic leukemia (ALL) at the Princess Noorah Oncology Center over 25 years was performed. A number of improvements were introduced over time including optimizing the cancer care delivery culture, improving access to care, optimizing supportive care, and refining diagnostic and therapeutic capabilities. Outcomes were evaluated over three time periods (period 1, 1989–2000; period 2, 2001–2007; and period 3, 2008–2014). These findings were compared with results of collaborative clinical trials (CCT). Results Of the 686 patients treated, the five‐year overall survival (OS) rate improved from 74% ± 2.7% in period 1 to 89.5% ± 2.3% in period 3 (P < 0.0001). Among all patients, the five‐year cumulative incidence of death decreased from 26% in period 1 to 10.5% in period 3 (P < 0.0001). This decrease was mainly due to reduction in the incidence of death from disease (P < 0.00001). In contrast, significant improvement in T‐cell ALL survival outcomes (P < 0.0001) was observed overtime (from period 1 to period 3) as a result of significant reduction in both toxic deaths (P = 0.005) and disease‐related deaths (P = 0.001). Conclusions Survival outcomes in Saudi Arabia have improved with five‐year OS rate now approaching 90%. However, further population‐based research is needed to understand variance in outcomes from those reported by CCT groups.