Genomics-driven precision medicine using targeted therapies requires advanced molecular diagnostic tests. Decisions about the use and reimbursement for such tests are increasingly being made on the basis of more outcome-based and value-based approaches. The value proposition concept is a tool to assess the benefits of laboratory testing to each stakeholder of the care pathway with respect to outcomes. This concept was applied to the use of noninvasive plasma epidermal growth factor receptor (EGFR) mutation testing in patients with advanced or metastatic non-small cell lung cancer (NSCLC) to guide treatment with EGFR tyrosine kinase inhibitors (TKIs). Using the value proposition framework, we evaluated published key evidence regarding clinical validity, economic implications, and limitations of this approach. It has been shown that plasma EGFR mutation testing is essential for guiding clinical decisions regarding prediction of eligibility of individual patients for TKI treatment, real-time monitoring, or adjustment of treatment regimens and tracking resistance. The appropriate use of plasma EGFR mutation testing has been shown to deliver both clinical and economic benefits to stakeholders across the entire care pathway; especially in clinical situations where biopsy material is inadequate or unavailable and where it leads to fewer tissue biopsies.