Introduction: Colorectal cancer is the third most common type of non-skin cancer in men (after prostate and Lung cancer) and women (after breast and Lung cancer). The mitochondrion conventionally is often thought to be an organelle specific to energy metabolism. It is in fact multifunctional and has been implicated in many diseases, including cancer. Alterations in the non-coding displacement loop of mitochondrial DNA are present in many types of cancer. In another word this loop has been shown to be a mutation "hot spot" in human cancers. Material and methods: To assess the relationship between mitochondrial DNA haplogroups and colorectal cancer, we sequenced the mitochondrial DNA hypervariable segment I in a study population that comprised 95 cases (55 male, 40 female) and 100 unrelated healthy individuals as a control groups. Haplotypes were assigned according to the West Eurasian mtDNA genealogy. Results: We found that haplogroup K is more frequent in colorectal patients than healthy individuals. That means haplogroup K is significantly more abundant in colorectal cancer patients (P=0.001). Conclusions: In this study we found a significant association of haplogroup K with colorectal cancer in Iranian patients so our finding suggests that mitochondrial genetic background plays a role in modifying an individual's risk for colorectal cancer. Copyright © 2008 Termedia & Banach.