['Cripto-1 (CR-1) is highly expressed in several different types of human tumors. However, the clinical significance of CR-1 expression in serum specimens from non-small cell lung cancer (NSCLC) patients has not yet been determined.', 'The aim of this study was to explore the diagnostic and prognostic value of serum CR-1 levels in patients with NSCLC.', 'Serum specimens from 592 NSCLC patients, 180 benign lung disease patients, and 240 healthy controls were collected. The concentrations of CR-1 were measured by sandwich enzyme-linked immunosorbent assay.', 'Patients with NSCLC had higher serum CR-1 levels than the controls (P<0.01) and patients with benign lung diseases (P<0.01). When a cutoff point of 1.8 ng/ml was selected (diagnostic specificity 95%), the diagnostic sensitivity for NSCLC is 56.8%. About 37.5% of CEA-negative lung cancer patients were CR-1 positive at 95% specificity. In patients with stage I/II lung cancer, use of these two markers in combination results in almost 21% increase in sensitivity, at 95% specificity, compared with CEA alone. Univariate analysis revealed that NSCLC patients with positive CR-1 had a shorter overall survival (OS) and progression-free survival (PFS) than those with negative CR-1 (HR of 2.93, P=0.005; HR of 2.12, P=0.005). Cox multivariate analysis indicated that CR-1 was an independent prognostic indicator of PFS and OS (HR of 1.91, P=0.006; HR of 1.82, P=0.007). Kaplan-Meier survival curves further confirmed that patients with negative CR-1 had longer PFS and OS (P=0.026 and P=0.011, respectively).'] Is serum Cripto-1 a novel biomarker for non-small cell lung cancer diagnosis and prognosis?