The current success of HER2 and MET targeted therapies using Trastuzumab (for cases with a HER2 amplification status) and Crizotinib in a combination manner in advanced and metastatic tumours including HER2 amplified and MET-mutant CUP tumours, suggest the further evaluation of these genes as druggable targets in patients with CUP46. Here, MET is linked to metastatic neoplasm.