Eph receptors compose the largest family of receptor tyrosine kinases (RTKs), which are capable of recognizing signals from the cell environment and influencing cell-cell interaction and cell migration. Ephrins are the ligands to Eph receptors and they stimulate bi-directional signaling of the Eph-ephrin axis. Ephrin-A3 (EFNA3) is one of the ephrin ligands which could bind to EphA2, EphA3, EphA5, EphA7, EphA8 and more poorly to EphA4. It is not only expressed in skeletal muscle, spleen, thymus, prostate, testis, ovary, small intestine and peripheral blood leukocytes, but is also present in neuroblastomas, neural cancers and leukemias. The dysregulated expression of EFNA3 has been observed in many types of human cancer. The expression level of EFNA3 was found to be upregulated 26-fold in squamous cell lung carcinoma, 3.8-fold in liver cancer, 1.6-fold in colon cancer and downregulated 2.6-fold in kidney carcinoma, respectively.