Deluged by a plethora of costly diagnostic tests, many stakeholders struggle to define criteria on which tests are appropriate to perform and in what settings. Appropriateness is often decided on the basis of expert opinion and some circumstantial evidence about diagnostic performance characteristics (eg, sensitivity and specificity). However, what really matters eventually concerns what happens to the patients undergoing the tests. What other tests, invasive procedures, or treatments were ordered or aborted based on the results? How were major clinical events, quality of life, or even survival (for serious conditions) affected? Did patients fare better because of the diagnostic drilling? Often, data to answer these questions are slim or nonexistent.