Background: The development of esophageal stricture during treatment with high dose chemotherapeutic agents is well known and documented in the literature. With the introduction of proton pumps inhibitors (PPI), the gastroesophageal reflux disease (GERD) induced stricture has shown significant improvement. The aim of this report is to remind of the fact that the chemotherapy induced strictures show poor response and their treatment is still a challenge. Case presentation: Here, we reported a boy with Down syndrome and congenital heart disease who developed acute lymphoblastic leukemia and subsequent esophageal stricture during treatment with a PPI. Conclusion: It is important to be aware of this potential complication of gastroesophageal reflux or antineoplastic treatment, even in cases thought to be adequately treated with a proton pump inhibitor, and that the start of PPI’s is also the start of an evaluation of the use of this medication.