BACKGROUND: Several value frameworks, including the American Society of Clinical Oncology (ASCO) Value Framework and National Comprehensive Cancer Network (NCCN) Evidence Blocks, have emerged in response to rising oncology drug costs and aim to assist stakeholders in assessing the value of oncology drugs. ASCO has developed a measure of clinical utility or value that it calls “net health benefit” (NHB), which represents a weighted measure of benefit-risk tradeoffs based on clinical benefit, toxicity, and bonus points. At the same time, the Institute for Clinical and Economic Review (I.C.E.R.) and the practitioners of cost-effectiveness analysis more generally use health outcomes modeling based on decision-analytic methods to produce estimates of NHB, in terms of life-years and quality-adjusted life-years, as the denominator of the incremental cost-effectiveness ratio. We ask: are they talking about the same thing? The answer is: “yes” and “no”. While the ASCO Value Framework and health outcomes model both produce an assessment of benefit-risk balance, they may generate very different weights on benefits and risks. To date, differences in NHB as reflected in the health outcomes modeling approach versus ASCO’s approach have not been fully explored. In this paper, we present an illustrative case study to highlight differences between the health outcomes decision-analytic modeling framework and the ASCO Value Framework in the benefit-risk assessment of a selected oncology drug in the advanced cancer setting. Scenario-based and sensitivity analyses are presented to demonstrate differences in how uncertainty in the NHB estimates can be assessed in the two frameworks. We examine the merits and contemporary challenges of implementing a quantitative health outcomes modeling approach to augment existing oncology value frameworks. Finally, we propose enhancements to existing value frameworks, including use of absolute effect measures and quantitative approaches to elicit preference weights, to improve their transparency and utility to various stakeholders.