BACKGROUND: The Quality of Life Utility - Core 10 Dimensions (QLU-C10D) is a disease-specific preference-based measure (PBM) designed to obtain health state utility values from patients with cancer. Previously, satisfactory psychometric properties were established from retrospective trial analyses using clinical anchors. This study aimed to validate the QLU-C10D against two generic PBMs in a prospective sample of Austrian and French patients with cancer using patient-reported anchors. METHODS: Patients completed the European Organisation of Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30), EQ-5D-5L and Short Form 36 (SF-36) at study baseline (any time during anti-cancer treatment) plus a follow-up assessment 3-6 months later. Sociodemographic and clinical characteristics were assessed. QLU-C10D and SF-6Dv2 utilities were calculated from QLQ-C30 and SF-36 data, respectively. German, French and UK value sets were applied for all three PBMs. Floor and ceiling effects were assessed. Known-group validity (independent t-test) and responsiveness (paired t-tests) were assessed respectively by ability to detect health status differences and changes over time according to patient-rated overall quality of life/health perception assessed by the QLQ-C30 Global Health Status scale, the EQ-5D-5L VAS and the SF-36 General Health scale. RESULTS: A total of 465 patients were included in the analysis. QLU-C10D index scores (intra-class correlation) and domains (Pearson) were correlated with EQ-5D-5L and Short-Form Six Dimensions (SF-6Dv2) conceptual counterparts. Correlation coefficients for the index scores of QLU-C10D and the generic PBMs ranged from 0.63 to 0.81. The QLU-C10D detected statistically significant differences between groups at baseline in 100% of tests performed (n = 27). For changes over time, QLU-C10D detected expected effects in 68% of cases (n = 29). In comparison with the generic PBMs, QLU-C10D detected differences and changes with a higher statistical efficiency in 76% of cases (77 of 102). CONCLUSIONS: The QLU-C10D is a fit-for-purpose ready-to-use PBM to estimate health state utilities of patients with cancer. This study adds to evidence that QLU-C10D has appropriate psychometric properties and appears to have higher statistical efficiency than generic PBMs in cancer.