The present invention relates to the field of the diagnostic of MSI cancer. In the present work, the inventors evaluated the performance of MSISensor for the detection of MSI in dMMR/MSI mCRC from multi center, prospective patients involved in clinical trials with ICI. The present analyse demonstrated that the FDA-approved NGS-based diagnostic test for identifying MSI in mCRC and nmCRC gave inaccurate results when compared with the gold standard reference methods. Consequently, whole exome sequencing (WES) data from all samples was further analyzed to improve detection of the MSI genomic signal in CRC and other primary tumor types. This allowed them to identify the weaknesses and limits of MSISensor and then to design and validate a newly optimized algorithm, namely MSICare. The high accuracy of MSICare for the detection of MSI in CRC and non-CRC tumors should allow it to become a future reference test for assessing MSI in pan-cancer. Thus, the present invention relates to a method of diagnosing an MSI cancer in a patient in need thereof comprising notably extracting and sequencing DNA from a tumoral sample and if available from a normal sample and operate an analyse of MNRs.