Two patients with RET-altered malignancies refractory to MKI therapy received selpercatinib on single-patient protocols: a patient with RET M918T-mutant medullary thyroid cancer presenting an acquired RET V804M gatekeeper mutation and a second patient with a KIF5B-RET fusion-positive NSCLC and symptomatic brain metastases. This evidence concerns the gene RET and medullary thyroid gland carcinoma.