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Introduction: In recent years, target therapies to specific molecular alterations in advanced non–small cell lung cancer (NSCLC) have been identified and have shown superior efficacy compared to non-targeted treatments. Anaplastic lymphoma kinase (ALK) is one of the therapeutic targets; nevertheless, ALK diagnosis is not performed in all NSCLC patients in Spain. The objective of this study is to estimate in monetary terms the benefit for the Spanish society of ALK diagnosis in advanced NSCLC patients. Methods: A cost-benefit analysis of ALK diagnosis vs. non-diagnosis in advanced NSCLC patients was carried out from the Spanish social perspective, with a time horizon of 5 years. Costs, benefits and the cost-benefit ratio weremeasured. The analysis has considered the overall survival in advanced NSCLC patients treated with the ALKtyrosine kinase inhibitor (TKI) alectinib. The natural history of NSCLC was simulated using a Markov model. A 3% discount rate was applied to both costs and benefits. The result was tested using a deterministic sensitivity analysis. Results: The cost of ALK diagnosis vs. non-diagnosis in the base case would be €10.19 million, generating benefits of €11.71 million. The cost-benefit ratio would be €1.15. In the sensitivity analysis, the cost-benefit ratio could range from €0.89 to €2.10. Conclusions: The results justify the universal application of ALK diagnosis in advanced NSCLC, which generates a benefit for Spanish society that outweighs its costs and allows optimal treatment with targeted therapies for these patients.