Endometrial carcinoma shows various histological types that differ in their clinical presentation and prognosis. Comparative genomic hybridization was used to detect gains and losses of DNA sequences along all chromosome arms in 24 uterine serous and 24 uterine endometrioid carcinomas. In serous carcinomas, extensive genetic aberrations were detected in 17 of the 24 specimens, with a mean of 5.7 changes per tumor. The most frequent gains occurred at 3q (50%), 8q (33%), 5p (29%), 6p (29%), and 1q (29%), and the most common losses were located at 4q (17%), 15q (17%), and 18q (17%). Tumors exhibiting DNA copy number changes were associated with shorter overall survival. In endometrioid carcinomas, genetic aberrations were less frequent and simpler than in serous carcinomas. DNA sequence copy number changes were observed in 12 of the 24 cases, with a mean of 1.5 changes per tumor. The most frequent aberrations were gains at 1q (29%), 2q (13%), and 8q (13%). Losses were rarely observed. The diverging pattern of genetic changes observed in uterine serous and endometrioid carcinomas suggests different pathways of carcinogenesis in these tumor types.