The article presents a clinical case of treating stage IV anaplastic thyroid cancer with a V600E mutation in the BRAF gene and distant metastasis (including metastases to the right ventricle of the heart and the right adrenal gland). At the first stage, targeted therapy (dabrafenib + trametinib) was performed, which allowed achieving pronounced clinico-metabolic regression and performing radical multi-stage surgical treatment. Subsequently, with the development of drug resistance and the detection of high expression of programmed cell death 1 ligand (PD-L1) (Combined Positive Score (CPS) – the ratio of the number of PD-L1-positive cells to the total number of tumor cells = 100), immunotargeted therapy with pembrolizumab in combination with lenvatinib was prescribed, resulting in a partial metabolic response. Despite the subsequent disease progression, overall survival from the time of diagnosis was 46 months. The presented clinical case demonstrates the importance of molecular profiling and the use of a multidisciplinary approach, as well as the possibility of using active surgical management in the oligoprogression of anaplastic thyroid cancer.