BACKGROUND: Currently biomarkers play an essential role in diagnosis, treatment, and management of cancer. In non-small cell lung cancer (NSCLC) determination of biomarkers such as ALK, EGFR, ROS1 or PD-L1 is mandatory for an adequate treatment decision. The aim of this study is to determine the clinical and economic impact of current anaplastic lymphoma kinase testing scenario in Spain. METHODS: A joint model, composed by decision-tree and Markov models, was developed to estimate the long-term health outcomes and costs of NSCLC patients, by comparing the current testing scenario for ALK in Spain vs a hypothetical no-testing. The current distribution of testing strategies for ALK determination and their sensitivity and specificity data were obtained from the literature. Treatment allocation based on the molecular testing result were defined by a panel of Spanish experts. To assess long-term effects of each treatment, 3-states Markov models were developed, where progression-free survival and overall survival curves were extrapolated using exponential models. Medical direct costs (expressed in €, 2019) were included. A lifetime horizon was used and a discount rate of 3% was applied for both costs and health effects. Several sensitivity analyses, both deterministic and probabilistic, were performed in order test the robustness of the analysis. RESULTS: We estimated a target population of 7628 NSCLC patients, including those with non-squamous histology and those with squamous carcinomas who were never smokers. Over the lifetime horizon, the current ALK testing scenario produced additional 5060 and 3906 life-years and quality-adjusted life-years (QALY), respectively, compared with the no-testing scenario. Total direct costs were increased up to € 51,319,053 for testing scenario. The incremental cost-effectiveness ratio was 10,142 €/QALY. The sensitivity analyses carried out confirmed the robustness of the base-case results, being the treatment allocation and the test accuracy (sensitivity and specificity data) the key drivers of the model. CONCLUSIONS: ALK testing in advanced NSCLC patients, non-squamous and never-smoker squamous, provides more than 3000 QALYs in Spain over a lifetime horizon. Comparing this gain in health outcomes with the incremental costs, the resulting incremental cost-effectiveness ratio reinforces that testing non-squamous and never-smoker squamous NSCLC is a cost-effective strategy in Spain.