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This study assessed the content validity of generic and condition-specific preference-based measures (PBMs) with patients treated for cancer, evaluated against 10 Consensus-Based Standards for the Selection of Health Measurement Instruments criteria for good content validity, to best inform measurement strategies regarding the use of PBMs in oncology development programs and real-world applications. Individual, semistructured interviews were conducted with patients who received drug treatment for cancer in the United Kingdom (n = 47) and the United States (n = 49). During the interview, patients completed 3 generic PBMs (EQ-5D-5L, EuroQol Health and Wellbeing measure–Short Form, Château Santé Base) and 2 condition-specific PBMs (Quality of Life Utility-Core 10 Dimension, Functional Assessment of Cancer Therapy Eight Dimension [FACT-8D]). Interviews were conducted via teleconference, audio recorded, and transcribed verbatim. Transcripts were coded using thematic and content analysis methods. Condition-specific measures were evaluated as having better relevancy than generic PBMs. Overall, the FACT-8D was evaluated as holding the best content validity in terms of relevancy, and the EuroQol Health and Wellbeing measure–Short Form received the most favorable evaluation of relevancy for generic PBMs. All measures demonstrated comparable comprehensiveness, with all suggested by patients to be missing concepts. The EQ-5D-5L was evaluated best in terms of comprehensibility. This was followed by the Quality of Life Utility-Core 10 Dimension and FACT-8D; both received similar evaluations. All measures were generally seen by patients as adequate in capturing appropriate aspects of health-related quality of life for measuring cancer outcomes, although together condition-specific measures were evaluated as having better relevancy than generic PBMs. Further health-related quality of life instrument development is encouraged, particularly with regard to the longer-term detrimental impacts of cancer and treatment side effects. Other developments could include new cancer-specific tools inclusive of conventional health items, treatment impacts, and psychological items. • Generic preference-based measures (PBMs) are recommended to assess patient-reported outcomes across interventions and to allow for comparative assessments across unrelated health conditions and interventions. Generic PBMs may exclude dimensions relevant to specific conditions, whereas condition-specific PBMs can contain items related to specific symptoms. Recent work has identified several concepts that are relevant to health-related quality of life and psychological wellbeing, which are not measured by existing outcome measures. • Patients who had received drug treatment for cancer in the United Kingdom and the United States evaluated 3 generic and 2 condition-specific PBMs during qualitative interviews. All measures demonstrated comparable comprehensiveness, missing concepts considered by patients as important to measure for their cancer and cancer treatment experiences. Language and format were frequently challenged, with patients suggesting changes to multiple items across all measures. Recall periods were frequently raised as problematic because of the substantial variation in cancer symptoms within a given day or week. • Given the burden of cancer symptoms and drug treatment effects, capturing all relevant outcomes of people with cancer is necessary to inform accurate decision making for cancer technologies. Modification of existing measures should be considered with regard to measurement gaps identified. New cancer-specific tools could be considered, inclusive of conventional health items, treatment impacts, and psychological items. These developments have a large potential for impact given the high proportions of oncology health technology assessment submissions. [ABSTRACT FROM AUTHOR]