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Hereditary Non-Polyposis Colorectal Cancer (HNPCC) is an autosomal dominant inherited condition characterized by an increased susceptibility to colorectal (CRC) and other associated cancers and defined by the Amsterdam I and II clinical criteria. An important fraction of these families is known as Lynch Syndrome and is caused by germline inactivating mutations in the mismatch repair (MMR) genes. This results in tumors that lack the corresponding proteins and fail to repair DNA through this pathway, causing microsatellite instability (MSI) and leading to an accumulation of somatic mutations. However, it is estimated that almost half of the families that fulfill the Amsterdam criteria do not present any defects in the MMR genes. For this reason, the term Familial Colorectal Cancer Type X (FCCTX) emerged to designate such group of HNPCC families that lack the MMR deficiency and resulting MSI that define Lynch Syndrome. Thus, FCCTX patients have microsatellite stable tumors with normal expression of the MMR genes, and the genetic basis underlying their predisposition to CRC and other related cancers remains to be elucidated...