Chromosomal aberrations play a dominant role in colorectal carcinogenesis. The application of fluorescence in situ hybridization (FISH) based techniques such as comparative genomic hybridization (CGH) and spectral karyotyping (SKY) revealed that colorectal carcinomas are characterized by a specific pattern of chromosomal imbalances which sequentially accumulate during cancer progression. This review aims to summarize molecular cytogenetic studies, provides a background on the functional relevance of chromosomal aberrations for colorectal cancer progression and discusses their potential clinical impact.