Herein, we present a case of a patient with stage IV LCNEC harboring a <i>KIF5B</i>-<i>RET</i> fusion whose disease responded to the selective RET inhibitor selpercatinib both extra- and intra-cranially, highlighting the importance of comprehensive molecular testing in LCNEC for selection of optimal treatment. Here, KIF5B is linked to large cell neuroendocrine carcinoma.