Endometrial carcinomas are common gynecological malignancies. Microsatellite instability and mismatch repair deficiency may be detected in endometrial carcinomas and tumours associated with Lynch syndrome. We aimed to compare results obtained using immunohistochemical mismatch repair (MMR) antibodies and polymerase chain reaction (PCR) for microsatellite instability (MSI) on endometrioid endometrial carcinomas (EEC) at a South African state hospital. Once ethical clearance was obtained, 145 cases of EEC were retrieved. These cases were subjected to immunohistochemistry (IHC) for MLH1, PMS2, MSH6 and MSH2 antibodies; and multiplex MSI PCR for the markers BAT-25, BAT-26, NR-27, NR-24, and NR-21. Cases demonstrating MMR and MSI discordance and cases showing loss of MLH1 staining then underwent MLH1 promoter methylation testing. Mismatch repair deficiency was noted in 28.28% of 145 cases, whilst 37.1% showed MSI by PCR. The overall accuracy was 69.29%. There were 37 cases showing loss of MLH1 staining and MMR/MSI discordance was detected in 25 cases. These cases underwent hypermethylation assessment which was identified in 72.13% of cases. The current study shows that 25 (17.24%) out of 145 cases would not have had abnormalities identified if PCR MSI had not been performed and would not have been flagged as having a possible germline mutation. Most (68%) of these 25 cases were hypermethylated. We therefore recommend that endometrial carcinomas undergo both screening tests in South Africa for patients under the age of 70 years. Tissue specimens may be tested for MSH6 and PMS2 immunohistochemical stains in addition to PCR MSI testing.