Nectins are immunoglobulin-like molecules that are involved in cell to cell adhesion by forming tight junctions and homophilic/heterophilic interactions. This study aimed to analyze serum nectin-2 and nectin-4 levels in lung cancer patients and to evaluate the prognostic, diagnostic and predictive strengths. Data from 74 lung cancer patients were retrospectively examined and enzyme-linked immunosorbent assays (ELISA) were used to measure serum nectin-2 and nectin-4 concentrations. A total number of 40 age and sex-adjusted healthy controls were also enrolled in the study. The median serum nectin-2 and nectin-4 levels of the patients were significantly higher than those of controls (p & x202f;< 0.001); however, neither biomarker was found to be associated with clinicopathological parameters, (p & x202f;> 0.05), and furthermore they were found not to be correlated with either overall survival or progression-free survival (p & x202f;> 0.05). Even though both markers showed high diagnostic values, serum nectin-2 was found superior to both serum nectin-4 and serum nectin-2 & x202f;+ nectin-4 combinations in the diagnosis of lung cancer according to higher sensitivity, specificity and predictive values. Serum nectin-2 and nectin-4 might be used in lung cancer diagnosis but the diagnostic importance of nectin-2 is higher. The prognostic and predictive strengths in cancer are controversial. Furthermore, the interactions with tumor microenvironments and the potentials as therapeutic targets for malignancies have yet to be elucidated.