Recent evidence in non-small cell lung cancer (NSCLC) about the new highly selective REarranged during Transfection (RET) inhibitors selpercatinib and pralsetinib, despite impressive results in clinical trials, have raised the urgency to highlight the best therapeutic sequence in view of novel resistances which are able to cause selective inhibition to be useless. The gene discussed is RET; the disease is non-small cell lung carcinoma.