Amplification of the human telomerase RNA component (TERC) gene was found in esophageal squamous cell carcinoma (ESCC). However, its roles in the progression and prognosis of ESCC have not been well understood. The amplification ofTERCin normal mucosa, low-grade and high-grade intraepithelial neoplasia, and invasive ESCC samples were evaluated using a fluorescence in situ hybridization assay. The amplification ofTERCinvariably occurred in high-grade intraepithelial neoplasia and invasive ESCC, partially occurred in low-grade intraepithelial neoplasia specimens, and seldom occurred in normal mucosa. The average signal ratio ofTERCto chromosome 3 centromere-specific probe (TERC/CSP3) was 1.00 ± 0.01 (average ± standard deviation) in normal mucosas, 1.01 ± 0.08 in low-grade intraepithelial neoplasias, 1.39 ± 0.26 in high-grade intraepithelial neoplasias, and 1.56 ± 0.41 in invasive ESCC. HighTERC/CSP3 ratio was positively associated with lymph node metastasis (P= 0.005) and advanced tumor stage (P= 0.045). Patients with high amplification ofTERChad poor survival (P= 0.01). The amplification ofTERCcould be used as a new genomic marker for disease progression and prognosis of ESCC. The amplifiedTERCgene may be a potential therapeutic target for ESCC.