Colorectal cancer (CRC) is the second most common malignancy as a cause of death in the western countries. Some of the genetic changes leading to colorectal cancer development are well characterised, such as frequent loss of chromosomes 5q, 17p, and 18q.1 These regions contain important tumour suppressor genes: APC in 5q, TP53 in 17p, and DPC4 / SMAD4 in 18q.2–4 These genes play a role in both somatic and hereditary tumorigenesis. Somatic mutations in APC , TP53 , and DPC4 / SMAD4 are frequently observed in sporadic CRCs. Germline mutations in APC predispose to familial adenomatous polyposis (FAP)2 and germline mutations in DPC4 / SMAD4 underlie juvenile polyposis.5 Both conditions are associated with CRC susceptibility. A recent twin study suggested that up to 35% of CRCs could have a predisposing genetic component.6 However, known mutations only account for 2–5% of all CRCs.7,8 Despite the growing knowledge about the genetic events underlying CRC, many of them are still unclear. Comparative genomic hybridisation (CGH) and loss of heterozygosity (LOH) analyses have shown that besides the above mentioned losses, whole or partial loss of chromosomes/chromosome arms 1p, 4, 8p, and 22 are recurrent aberrations in colorectal tumours.9–11 This suggests that genes that have a key role in colorectal tumorigenesis reside in these chromosomes. Recent studies have shown evidence of the role of mutations in genes associated with mitochondrial energy metabolism in the pathogenesis of different tumour types. Germline mutations affecting the B, C, and D subunits of succinate dehydrogenase (SDH) cause hereditary paragangliomas.12–14 Carriers of mutations affecting the B subunit of SDH can occasionally develop phaeochromocytomas.14 A novel cancer predisposition syndrome, hereditary leiomyomatosis and renal cell cancer (HLRCC), is caused by germline mutations in the fumarate hydratase gene ( FH ). …