Introduction: Microsatellite instability (MSI) is defined as accumulation of mutations in short repeated DNA sequences (1 to 9 nucleotides) that occurs at genomic regions called microsatellites (MS), also known as short tandem repeats (STR) leading to a state of genomic instability which predispose to neoplastic transformation. MSI occurs as a result of generation of uncorrected DNA slippage or DNA mismatch during replication in dMMR cells leading to a state of genomic instability which predispose to neoplastic transformation. MSI was primarily studied in colorectal and other Lynch syndrome-associated tumours. Advances in sequencing technologies have demonstrated that MSI plays a key role in non-Lynch-associated tumours as well. The clinical utility of MSI testing has been expanded rampantly in personalized medicine from a favourable prognostic marker, to predict the ineffectiveness to chemotherapy, as a hall mark of Lynch syndrome. In the era of immunotherapy, MSI is a key albeit rare indication and patients with dMMR have shown exceptional responses to immune check inhibitors (ICI) therapy (dostarlimab response in EC). Elevated MSI is a pan-cancer tumour agnostic marker for immunotherapy and included in both NCCN and ESMO guidelines.Materials and Methods: A retrospective cross-sectional study of all histopathologically proven carcinomas in patients with cancer (n=329) in all organ systems who underwent MSI testing by PCR and fragment analysis was analysed from January 2019 to March 2023 in tertiary care hospital in India. All the samples were subjected to laboratory developed assay for PCR amplification and fragment analysis by capillary electrophoresis using a set of 5 mononucleotide markers (BAT25, BAT-26, NR-21, NR-24 and NR-27) for the presence of instability. The sensitivity of the assay was limited to 10% tumour content and 5% mutant allele. Clinicopathological characteristics like age, sex and TNM staging were compared to MSI results, and its role in modifying the treatment or personalized medicine was evaluated. Patient characteristics were compared using t tests for continuous variables, p value less than 0.05 and chi-square. The results were analysed using SPSS software.Results: Of the total 329 patients tested for microsatellite instability (MSI), 47 patients were found to be MSI-High, 5 patients were MSI-Low and 277 of them were MSI-Stable. Among the MSI-High cases, 35 patients were observed to found in colorectal cancers (total N = 194), 6 in endometrial cancer (total N = 35), 2 in stomach cancers (total N = 38), 1 each in ovary (total N = 7), cervix (total N = 4), oesophagus (total N = 10) and gall bladder (total N = 3) cancers. Of the 5 MSI-Low cancers, three patients were seen in colorectal (total N = 194) and one each in endometrium (total N = 35) and ovarian cancers (total N = 7). The median age range among all cancers was found between 32 and 78 years. In colorectal cancers, the incidence of MSI-High was found more in females as compared to males. The chemotherapy could be avoided in 88% of the patient of stage II CRC and three patients of CRC in stage IV were started on immunotherapy.Conclusion: The study provides clinico-epidemiological insights into MSI testing and prevalence of MSI with emphasis on specific cancer subtypes. It has been known to be good prognostic marker in solid tumours. MSI patients respond poorly to chemotherapy and could be avoided in 88% of the patient of stage II CRC. Additionally, MSI testing may provide cost and outcome benefits with ICI initiation instead of standard CT/RT in metastatic settings.