We also report case studies from the MSKCC clinical cohort demonstrating exceptional clinical responses to HER2-targeted therapies in a patient with NSCLC with a TMD mutation and in two patients with non-NSCLC and ERBB2 mutations, all negative for ERBB2 amplification/overexpression, as proof of principle that a wider lens should be used in determining eligibility for treatment with HER2-directed agents. The gene discussed is ERBB2; the disease is non-small cell lung carcinoma.