The objective of this study was to compare the sensitivity to CPT-11 in a series of CRC cell lines classified based on the microsatellite and the mutational status in coding mononucleotide repeats of MRE11 and RAD50. Additionally, we aimed to assess the differences in sensitivity between cell lines with a genetic mutation in MMR genes (MLH1 or MSH6), which resemble HNPCC, and cell lines with silencing of the hMLH1 gene due to the promoter hypermethylation, such as sporadic MSI-H CRC cases. This evidence concerns the gene MRC1 and colorectal carcinoma.