Endometrial carcinoma (EC) is the world’s most common gynaecological malignancy and the fourth most common carcinoma in females. Microsatellite instability high/mismatch repair deficient (MSI-H/dMMR) EC is the most represented EC subtype and is strongly associated with higher expression of anti-programmed death 1 (PD-1) receptor levels, potentially making these tumours responsive to anti-PD-1 treatment. This case report describes the screening and treatment strategies of a 67-year-old female diagnosed with EC, which was initially treated with adjuvant therapy with chemotherapy and radiotherapy (RT). However, after the emergence of a secondary tumour lesion in the brain and other secondary body lesions, the patient started dostarlimab therapy (an anti-PD-1 monoclonal antibody) combined with RT, to evaluate a possible synergistic immune-mediated anti-tumour effect. After 5 months of therapy, the instrumental follow-up showed a complete brain lesion response, and 5 months later, a partial response of the body lesions too. In conclusion, this case report outcome supports the combination of RT and immunotherapy to control and manage MSI-H/dMMR ECs.