Herein, we report a case of relapsed advanced <i>ERBB2</i>-mutant NSCLC with acquired resistance to zongertinib potentially mediated through <i>ERBB2</i> amplification and <i>HER2</i> 3+ immunohistochemistry overexpression with subsequent durable response to fifth-line trastuzumab-deruxtecan. Here, ERBB2 is linked to non-small cell lung carcinoma.