Microsatellite instability (MSI) is a molecular scar resulting from a defective mismatch repair system (dMMR) and associated with various malignancies. MSI tumours are characterized by the accumulation of mutations throughout the genome and particularly clustered in highly repetitive microsatellite (MS) regions. MSI/dMMR status is routinely assessed in solid tumours for the initial screening of Lynch syndrome, the evaluation of cancer prognosis, and treatment decision-making. Currently, pentaplex PCR-based methods and MMR immunohistochemistry on tumour tissue samples are the standard diagnostic methods for MSI/dMMR. Other tissue methods such as next-generation sequencing or real-time PCR-based systems have emerged and represent viable alternatives to standard MSI testing in specific settings. The evolution of the standard molecular techniques has offered the opportunity to extend MSI determination to liquid biopsy based on the analysis of cell-free DNA (cfDNA) in plasma. This review aims at synthetizing the standard and emerging techniques used on tumour tissue samples for MSI/dMMR determination. We also provide insights into the MSI molecular techniques compatible with liquid biopsy and the potential clinical consequences for patients with solid cancers.