Lung cancer remains the leading cause of cancer related mortality worldwide. We aimed to test whether a simple blood biomarker (extracellular vesicle miRNAs) can discriminate between cases with and without lung cancer. Methods: plasma extracellular vesicles (EVs) were isolated from four cohorts (n = 20 in each): healthy non‐smokers, healthy smokers, lung cancer, and stable COPD participants. EV miRNA expression was evaluated using the miRCURY LNA miRNA Se-rum/Plasma assay for 179 specific targets. Significantly dysregulated miRNAs were assessed for discriminatory power using ROC curve analysis. Results: 15 miRNAs were differentially expressed between lung cancer and healthy non‐smoking participants, with the greatest single miRNA being miR‐205‐5p (AUC 0.850), improving to AUC 0.993 in combination with miR‐199a‐5p. Moreover, 26 miRNAs were significantly dysregulated between lung cancer and healthy smoking participants, with the greatest single miRNA being miR‐497‐5p (AUC 0.873), improving to AUC 0.953 in combination with miR‐22‐5p; 14 miRNAs were significantly dysregulated between lung cancer and stable COPD participants, with the greatest single miRNA being miR‐27a‐3p (AUC 0.803), with two other miRNAs (miR‐106b‐3p and miR‐361‐5p) further improving discriminatory power (AUC 0.870). Conclusion: this case control study suggests miRNAs in EVs from plasma holds key biological information specific for lung cancer and warrants further prospective assessment.