Adenocarcinoma of the pancreas is the fifth most common cause of cancer deaths in the United States, yet few cytogenetic studies of this tumor have been reported. We analyzed 26 primary tumors to identify which chromosome abnormalities occur most frequently in this neoplasm. One carcinoma was well differentiated and mucin producing, 18 were moderately well differentiated, and seven were poorly differentiated. Only normal karyotypes were obtained from nine carcinomas. The remaining 17 carcinomas frequently had normal metaphase cells in addition to simple to highly complex karyotypes. The modal chromosome number in 20 carcinomas was diploid or near-diploid; four carcinomas had both a major near-diploid and near-triploid or near-tetraploid component, and two were near-tetraploid. Numerical abnormalities included loss of whole copies of chromosomes 6, 17, and 18, and gains of chromosome 20. Structural abnormalities were frequent, with 1p, 2p, 3p, 4q, 6q, 7q, 11q, and 17p recurrently involved. Results of this study were combined with karyotypes of 19 other primary adenocarcinomas of the pancreas reported in the literature. The combined data involving 117 breakpoints suggest that careful analysis of chromosome 20, proximal 1q, 6q, proximal 8p, and proximal 17p could be productive in defining genes involved in adenocarcinoma of the pancreas.