This study explored the relationships between health-related quality of life (HRQoL) and tumor biology in a trials setting. Tumors were categorized into the SHH, WNT and non-SHH/non-WNT subgroups. The distribution of scores for quality of survival, at a mean interval of 7 years from diagnosis using the health utilities index total utility score, the Strengths and Difficulties Questionnaire, and the pediatric quality of life inventory total score, showed differences in patterns between tumor molecular subgroups. In spite of WNT patients displaying a better prognosis, the analysis indicated that patients with SHH subgroup tumors are associated with better parent-report HRQoL. The larger effect on parent- than self-report of HRQoL is consistent with the larger effects reported by parents in all 108 patients that participated in the PNET3 QoS study.