This study aimed to identify the status of 2 major microsatellite instability markers (repair genes hMSH2 and hMSH6) in colorectal cancer cases operated at King Khalid University Hospital, Riyadh, Saudi Arabia between 2007 and 2009. Immunohistochemical study of microsatellite instability was done with antibodies to hMSH2 and hMSH6. A total of 32 blocks were analysed from patients aged 16-83 years (median 56 years); 14 blocks (43.8%) were from resections and 18 (56.2%) were from biopsies. An adenomatous component was present in 4 (12.5%) blocks. The colonic carcinoma, the adenomas and the normal tissue showed strong nuclear reactivity to hMSH2 and hMSH6 in 96.9% of the cases. The rate of loss of expression was 3.1%. The rate of mutation in our sampled population was low and matched the rate reported in the literature from industrialized countries. Further studies are needed to confirm the use of these markers in the diagnosis of colorectal cancer.