The incidence of cancer in children with intellectual disability has been poorly documented. We report our experience of treating children and adolescents with cancer and intellectual disability (40 patients), from 2004 to 2018. A treatment-sparing approach was adopted for 6 patients with severe intellectual impairment to minimize toxicity: a child with postpartum asphyxia and medulloblastoma did not receive radiotherapy; 1 patient with mitochondrial encephalopathy and a testicular germ cell tumor did not receive bleomycin and lung metastasectomy; 2 patients (1 with Down + West syndrome + Wilms tumor (WT) and 1 with Denys-Drash syndrome + WT) did not receive vincristine; 1 child with corpus callosum agenesis and anaplastic ependymoma did not receive chemotherapy; 1 child with structural chromosomal aberrations and a primitive neuro-ectodermal tumor received personalized chemotherapy. Heminephrectomy was performed in 4 patients with WT to preserve their kidney function. We found no statistically significant correlation between relapse or mortality rates and the use of a treatment-sparing approach. The 5-year overall survival (OS) and event-free survival (EFS) rates were 184.108.40.206.9 respectively, for patients in our usual-treatment and treatment-sparing groups.Conclusion: We only opted for a treatment-sparing approach for patients with severe disabilities, and their OS was in line with that of children without intellectual disability. What is Known: • There are few reports on children/adolescents with cancer and intellectual disability (ID). • It is not clear how to manage them and whether a treatment sparing should be considered, especially in the case of severe disability. What is New: • Most patients received the standard cancer treatment and only in the case of severe disability, a therapeutic saving approach was applied. • No statistically significant correlations between relapse/mortality rates and the use of a treatment-sparing approach were found.