Sixty primary esophageal squamous cell carcinomas (ESCCs) were evaluated for cytogenetic changes by comparative genomic hybridization (CGH). Recurrent chromosomal aberrations were correlated with stage and clinical outcome after esophagectomy to identify cytogenetic changes that are of prognostic significance. Chromosomal aberrations were found in 52 (86.7%) cases. The most frequently detected chromosomal gains involved 3q (67.3%), 8q (57.7%), 5p (51.9%), 7q (28.8%), 15q (28.8%), 20p (21.2%), 20q (28.8%), 1q (26.9%), 7p (26.9%), 2p (23.1%), and 12p (23.1%). Chromosome 12p was most frequently involved in high-level amplification. Six of the 12 cases with gain in 12p showed high-level amplification and the minimum overlapping region localized to 12pter-p13. The most frequently detected chromosomal loss involved 3p (46.2%), 4q (26.9%), 4p (23.1%), 3q (19.2%), 9p (17.3%), 19p (17.3%), and whole 13 (15.4%). No significant correlation was found between the recurrent chromosomal aberrations and pathological stage of ESCC. Univariate analysis demonstrated that late pathological stage (III and IV), gain in 12p, and loss in 3p are associated with poor relapse-free survival. Multivariate analysis confirmed gain in 12p as independent prognosticator for relapse-free survival after esophagectomy besides pathological stage. We conclude that chromosomal aberrations are common in ESCC. Gain in 12p is indicative of poor prognosis after esophagectomy, and combined modality therapy would be indicated in these patients.