OBJECTIVES: Our aim was to produce a white paper that identifies key issues facing the HTA of complementary diagnostics in Europe, defines options for addressing challenges and barriers, and recommends approaches for dealing with them METHODS: (1) Systematic literature review on different value frameworks and specific valuations for complementary diagnostics. (2) Analyses of health economic evaluations of three complementary diagnostics presented by the HTA agencies of England (National Institute of Health and Care Excellence, NICE) and France (Haute Autorité de Santé,  HAS), where available RESULTS: We distinguish among seven elements of value for complementary diagnostics which are independent and additive and that should be considered aggregated at societal level. Three are included in the traditional cost-effectiveness analysis conducted as part of HTA (life years gained; improvements in patient quality of life; cost savings within the healthcare system (also called “cost-offsets”)). The fourth is “productivity”. We identified three other potential sources of value in healthcare technologies that are also relevant to complementary diagnostics: reduction in uncertainty (value of knowing/planning value); option value/value of hope; and scientific spillovers CONCLUSIONS: The full value that complementary diagnostics can bring to patient care is underappreciated in healthcare systems around the world.  By identifying those unique elements of value related to information, we aim not only to increase appreciation but also to provide a basis for evaluating and valuing their impact.  As these healthcare systems evolve to more accountability for outcomes and to value-based reimbursement, the framework described here should provide a sounder basis for the HTA of complementary diagnostics as well as for appropriate reimbursement and rewards for innovation