To better understand the biological functions of Eph/ephrin genes in human lung carcinomas, mRNA expression levels of EphA2， EphB，EphB4，ephrin-A5 and ephrin-B2 were quantified in samples from 48 non-small-cell lung carcinomas (NSCLCs) in comparison with normal lung tissues by real-time PCR assay. The up-regulations of EphB4, EphB3 and ephrin-A5 in 27 of 48(60%), 39 of 48(81%) and 31 of 48(65%) lung cancers were found respectively. The results also showed that the expression of ephrin-A5 gene is associated with tumor histology, tumor size, metastasis, gender, smoking habits and age of the patients. There is a significant correlation between EphA2 expression and tumor size, tumor age and family history. All these results suggest that EphB4, EphA2, EphB3 and ephrin-A5 might function independently or synergistically in initiation and progression of primary lung cancer, and they might serve as valuable targets for therapeutic intervention.