Two forms of genetic instability have been described in colorectal cancer: chromosomal instability, characterized by structural and numerical chromosomal abnormalities and associated to aneuploidy; and microsatellite instability, characterized by a deficiency in the mismatch repair system that leads to slippage in microsatellites and is associated to euploidy. Thirteen colorectal cancer sample DNAs were analyzed after colectomy. High-resolution genome-wide DNA copy number and Single Nucleotide Polimorphism genotyping analysis was performed by Affymetrix SNP 6.0 arrays that interrogates 906,600 single nucleotide polymorphisms and 945,826 copy number probes. We implemented this analysis as part of a routine procedure that includes the sampling of fresh tissue from the tumor mass without affecting the subsequent standard histopathological procedure. The novel molecular technology allows the determination of a genome-wide molecular karyotype using only 500 ng of high-quality tumor DNA; it distinguishes the two main types of genomic instability, discriminating between chromosomal instability positive and negative tumors. It also detects loss of heterozygosity (LOH) regions, called copy neutral-LOH. Tumor-associated copy neutral-LOH regions may play a pivotal role in oncogenesis when they determine duplications of either activating or loss of function gene mutation. We observed recurrent gains of chromosomes 2, 7, 8q, 9, 12, 13, 20 and losses of chromosomes 4, 5, 8p, 15, 17p, 18, 22, and Y, in agreement with previous cytogenetic studies. The use of such sampling procedure could stimulate the routine detection of point mutations in specific genes, thus avoiding subsequent sectioning of formalin-fixed and paraffin-embedded samples.