Colorectal cancer still represents a paradigm for the elucidation of the cellular, genetic and molecular mechanisms that underly solid tumor initiation, progression to malignancy, and metastasis to distal organ sites. The relative ease with which pathological specimens can be obtained by either surgery or endoscopy from different stages of tumor progression has facilitated the application of omics technologies to allow the genome-wide analysis both at the RNA (gene expression) and DNA (aneuploidy) levels. Here, we have reviewed the multiplicity of studies appeared to date in the scientific literature on the expression and genomic analysis of colorectal cancer, and attempted an integration of the profiling data generated and made available in the public domain. This approach is likely to pinpoint specific chromosomal loci and the corresponding genes which (i) play rate-limiting roles in colorectal cancer, (ii) represent putative diagnostic and prognostic markers for the accurate prediction of clinical outcome and response to treatment, and (iii) encompass potential therapeutic targets. Moreover, cross-species data mining and integration of the human colorectal cancer profiles with those obtained from mouse models of intestinal tumorigenesis will even more contribute to the elucidation of highly conserved pathways and cellular functions underlying malignancy in the GI tract. Notwithstanding the above promises, tumor heterogeneity, limited cohort sizes, and methodological differences among experimental and bioinformatic approaches still poses main obstacles towards the optimal utilization and integration of omics profiles.