A patient presenting with metastatic MTC associated with somatic RET D898_E901del was treated with selpercatinib after thyroidectomy and neck dissection; disease progression at 24 months associated with ETV6::NTRK3 fusion was treated with larotrectinib in addition to selpercatinib; further disease progression after another nine months associated with EML4::ALK fusion was treated by switching from larotrectinib to entrectinib; unfortunately, further progression associated with NTRK3 G623R ultimately led to treatment failure. The gene discussed is RET; the disease is medullary thyroid gland carcinoma.