Abstract: To investigate the effects of genetic polymorphisms and alterations in methylation patterns on oncogenesis and progression of esophageal cancer. Methods: a) Six polymorphic sites (AR, Rb17, Rb16, ER- pvuⅡ, ER- XbaI and cbl2) from the cancerous and paraneoplastic tissues from 35 patients with esophageal squamous cell cancer (ESCC) were analyzed using polymerase chain reaction- amplified fragment length polymorphism (PCR- AFLP) and Genescan software. b) The genomic methylation level in the cancerous and paraneoplastic tissues was assayed using HPLC. Results: Alteration of at least one site occurred in 26 of the 35 patients (74.3%). The changes at the polymorphic site in different stages were as follows: 9/12 (75%) in stage Ⅰ, 13/15 (85%) in stage Ⅱ, and 4/8 (50%) in stage Ⅲ. The total genomic DNA methylation level in early esophageal cancer was lower than that of the paraneoplastic tissues, but it surpassed the paraneoplastic tissues as the methylation level gradually increased with the process of tumor cell differentiation. Conclusions: It is presumed that genetic instability is a common event in the genesis and development of esophageal carcinoma. Genomic instability in esophageal carcinoma may be related to the decreased genomic methylation in patients with early esophageal cancer.