BACKGROUND: It is not clear if good methodologic quality in current practice guidelines necessarily leads to more valid recommendations, i.e., those that are supported with consistent research evidence or, when evidence is conflicting or lacking, with sufficient consensus among the guideline development team. To help clarify this issue, we assessed whether there is a link between methodologic quality and recommendation validity in practice guidelines for the use of laboratory tests in the management of patients with non-small cell lung cancer (NSCLC). METHODS: We conducted a systematic review of data on laboratory tests in NSCLC published in English or in French within the last 10 years and retrieved 11 practice guidelines for the use of these tests. The guidelines were critically appraised and scored for methodologic quality and recommendation validity based on the Appraisal of Guidelines Research and Evaluation (AGREE) criteria and on the systematic review. RESULTS: Overall, these 11 guidelines had considerable shortcomings in methodologic quality and, to a lesser extent, in recommendation validity. Practice guidelines with the best methodologic quality were not necessarily the most valid in their recommendations, and conversely. CONCLUSIONS: Poor methodologic quality and lack of recommendation validity in laboratory medicine call for methodologic standards of guideline development and for international collaboration of guideline development agencies. We advise readers of guidelines to critically evaluate the methods used as well as the content of the recommendations before adopting them for use in practice.