OBJECTIVES There is a growing need for early evaluation of innovative technologies to prevent ineffective and expensive technologies to be widely diffused in health care. The headroom method was introduced for early determination of the potential value of new technologies. In this study we explore the feasibility and usefulness of the headroom method in the early assessment of diagnostic technologies with no immediate treatment implications.  METHODS We applied the headroom method to the implementation of whole exome sequencing (WES) into the current diagnostic trajectory of complex pediatric neurology. We determined the room for improvement regarding health-related quality of life (HRQoL), diagnostic yield and the duration of the current diagnostic trajectory. RESULTS The headroom in a certain diagnostic trajectory can be calculated after the so-called effectiveness gap is established and monetised. The preferred measure for the effectiveness gap is HRQoL expressed in quality-adjusted life years (QALYs). Since the direct product of diagnostics is information, and not improved health, no impact on HRQoL is expected. Other measures, such as diagnostic yield, can also be used to calculate the effectiveness gap. Unlike QALYs, these appeared difficult to monetise, however. Despite this difficulty, effectiveness gap calculation using these effect measures is very informative on the room for improvement in current clinical practice. In combination with foreseeable downstream costs and savings due to a new technology it gives an idea of the potential societal value of this technology. CONCLUSIONS Despite some methodological challenges, the headroom method proved to be potentially useful in early health economic evaluation of diagnostic technologies with no immediate treatment implications.