We compared whole genomic changes in cell lines generated from esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). To do so, we investigated chromosomal DNA copy number changes in four EAC cell lines and three ESCC cell lines using comparative genomic hybridization (CGH). Frequent gains of chromosome 5p, 8q, and 20q occurred in both ESCC and EAC cell lines, but gains of 3q, 5q, and 9q were mainly seen in ESCC cell lines; gain of chromosome 10q25-qtel was mainly seen in EAC cell lines. It was noticeable that 18q12 loss existed in 2 EAC and 1 ESCC cell lines in our study. The chromosomal abnormalities common to all of the cell lines may help to identify candidate genes related to both EAC and ESCC. The chromosome aberrations mainly seen in either EAC or ESCC cell lines are in keeping with their known different etiology and may lead to the identification of genes important for disease specific pathogenesis.