HER3 is ubiquitously expressed in EGFR-mutant non-small cell lung cancer (NSCLC) irrespective of resistant mechanisms to EGFR tyrosine kinase inhibitors, thus garnering attention as a valuable therapeutic target. In this issue of Cancer Discovery, Jänne and colleagues highlight early clinical data supporting patritumab deruxtecan as a potentially appreciable agent for previously treated EGFR-mutant NSCLC.See related article by Jänne et al., p. 74.