Cytogenetic changes are widely unknown for nonpolypoid (synonymously termed as “flat” or “depressed”) colorectal adenomas. A comparison with polypoid adenomas will contribute to the discussion whether different genetic pathways for colorectal tumorigenesis depending on its origin from nonpolypoid or polypoid adenomas exist. Tissue samples of nonpolypoid (n = 22), polypoid (n = 28) adenomas, carcinomas ex-nonpolypoid adenomas (n = 9), carcinomas ex-polypoid adenomas (n = 14), and normal colonic mucosa (n = 9) were investigated by comparative genomic hybridization of whole genomic DNA. Chromosomal imbalances were detected from average comparative genomic hybridization profiles for each entity. Nonpolypoid adenomas show recurrent chromosomal losses on chromosomes 16, 17p, 18, 20, and 22 and gains on chromosomes 2q, 4q, 5, 6, 8q, 12q, and 13q. In polypoid adenomas losses of whole chromosomes 16, 18, and 22 and gains of chromosomes 7q and 13 were detected. The frequency of copy number changes was higher in nonpolypoid compared to polypoid adenomas and early onset of chromosomal changes became apparent in low-grade dysplasias of nonpolypoid adenomas. Gains on chromosomes 2q, 5, 6, 8q, and 12q and losses on chromosomes 17p and 20 occurred exclusively in nonpolypoid adenomas, whereas 16p deletions are significantly more frequent in nonpolypoid than in polypoid adenomas. Carcinomas ex-nonpolypoid adenomas are characterized by more complex aberration patterns compared to nonpolypoid adenomas exhibiting frequent losses on chromosomes 8p, 12q, 14, 15q, 16, 17p, 18, and 22 and gains on 3q, 5, 6, 7, 8q, 12q, and 13, respectively. Normal colonic mucosa showed no chromosomal imbalances. Distinct differences of chromosomal imbalances between nonpolypoid and polypoid colorectal adenomas have been characterized that support the hypothesis that different genetic pathways may exist in the development of colorectal adenomas exhibiting nonpolypoid and polypoid phenotype.