BACKGROUND AND OBJECTIVES: Molecular genetic testing using tissue biopsies can be challenging for patients due to unfavorable tumor sites, the invasive nature of a tissue biopsy, and the added time of booking a repeat biopsy (re-biopsy). Centers in Canada have found insufficient tissue rates to be approximately 10%, and even among successful biopsies, insufficient DNA in tissue samples is approximately 16%, triggering the lengthy process of re-biopsies. Using aNSCLC as an example, this study sought to characterize the health and budget impact of alternative liquid-biopsy(LBx)-based comprehensive genomic profile (CGP) testing in tissue-limited patients (TL-LBx-CGP) from a Canadian publicly funded healthcare perspective. MATERIAL AND METHODS: An economic model was developed to estimate the incremental cost and life-years gained as a population associated with adopting TL-LBx-CGP. The eligible patient population was modeled using a top-down epidemiological approach based on the published literature and expert clinician input. Treatment allocation was modeled based on biomarker prevalence in the published literature, and the availability of funded therapies. Costs included molecular testing, as well as drug, administrative, and supportive costs, and relevant health data included median overall survival and median progression-free survival data. RESULTS: Incorporation of TL-LBx-CGP demonstrated an overall impact of $14.7 million with 168 life-years gained to the Canadian publicly funded healthcare system in the 3-year time horizon.