It is generally accepted that colorectal cancer (CRC) can progress through either chromosomal instability (CIN) or microsatellite instability (MSI). We evaluated the pattern of genomic instability in 91 sporadic colorectal cancer patients by analyzing the MSI status and loss of heterozygosity (LOH), as evidence for CIN, in 8 microsatellite markers located on chromosomal arms 2p, 3p, 5q, 17p and 18q. Five of the markers were from the NCI-recommended panel for MSI testing, while the others were located in the regions harboring tumor suppressor (APC, p53) or mismatch repair (MLH1, MSH2) genes important for CRC development. MSI was detected in 11 cancers (12.1%) that were primarily located in the right colon, with mucinous histotype and lower stage at diagnosis. The LOH of at least one chromosomal arm was detected in 57 (62.3%) of cancers, of which the most common was 18q (84.2%) followed by 5p (54.4%) and 17p (45.6%). Four out of 11 patients from the MSI group also exhibited LOH of at least one chromosomal arm indicating a significant overlap between the two types of genomic instabilities. In 27 patients (29.67%) we didn’t detect any evidence of CIN or MSI. Our data indicate a significant overlap between CIN and MSI phenotypes and suggest that in almost 1/3 of all cases the molecular mechanism is not related to either CIN or MSI type of genomic instability.