Gene overexpression most frequently affects oncogenes such as YES1,TYMS, HEC, TGIF, NCOA3, BTAK, DCR3, E2F1, MYC, EGFR, EGR2, CCND, FGF3/FGF4, EMS1, SAS, ERBB2, PDGFR1, BCL2, MDS1 and PRKCI, whereas genomic losses lead to the deletion of suppressor tumor genes such as CDKN2A, MTAP and TP53. Identification of the role of these critical genes in esophageal carcinogenesis will assist the development of individualized target therapy that should in turn improve the clinical outcome of ESCC patients. The gene discussed is FGF4; the disease is esophageal squamous cell carcinoma.