INTRODUCTION: Many health economic evaluations rely on the validity of the utility measurement for health-related quality of life (HRQoL). While generic utility measures perform well in HRQoL assessments of many diseases and patient populations, appropriateness for cancer-specific disease burdens needs attention and condition-specific measures could be a viable option. This study assessed the clinical validity of the cancer-specific EORTC QLU-C10D, a utility scoring algorithm for the EORTC QLQ-C30, in patients with glioblastoma. We expect the EORTC QLU-C10D to be sensitive and responsive in glioblastoma patients. Furthermore, we compared its statistical efficiency with the generic utility measure EQ-5D-3L. METHODS: We used data from a multi-center randomized controlled trial (NCT00689221) with patients from 146 study sites in 25 countries. Both, the QLQ-C30 and the EQ-5D-3L, had been administered at seven assessment points together. Utilities of both measures were calculated for four country value set (Australia, Canada, UK, USA). Ceiling effects, agreement (Bland-Altman plots (BA), intra-class correlation (ICC)), were calculated to analyze construct validity. Sensitivity to known-groups (performance status; global health) and responsiveness to changes (progressive vs. non-progressive; stable vs. improved or deteriorated HRQoL) were investigated for clinical validity. Relative Efficiency (RE) was calculated to compare statistical efficiency of both utility measures. RESULTS: 435 patients were included at baseline and six subsequent time points (median timeframe 497 days). QLU-C10D country value set showed negligible ceiling effects (< 6.7%) and high agreement with EQ-5D-3L (ICC > 0.750). BA indicated that differences between both utility measures increased with deteriorating health states. While the QLU-C10D was more sensitive to global health groups (RE > 1.2), the EQ-5D-3L was more sensitive to performance status groups (RE < 0.7) than the other utility measure. Statistical efficiency to detect differences between change groups and within HRQoL deterioration group (RE > 1.4) favored QLU-C10D in 18 of 24 (75%) and 20 of 24 (83%) comparisons with the EQ-5D-3L respectively. Responsiveness to overall HRQoL change (RE > 3.4) also favored the QLU-C10D. CONCLUSION: Our results indicate that the QLU-C10D is a valid utility measure to assess HRQoL in patients with glioblastoma. This facilitates the investigation of HRQoL profiles and utilities in this patient population by administering a single questionnaire, the EORTC QLQ-C30. Efficiency analyses point to higher statistical power of the QLU-C10D compared to the EQ-5D-3L.