In contrast to large-cell carcinoma (LCC) and large-cell neuroendocrine carcinoma (LCNEC), which currently lack well-established molecularly targeted approaches and are mainly treated with chemotherapy-based strategies, non-small-cell lung cancer (particularly the adenocarcinoma subtype) with oncogenic driver mutations such as EGFR represents a distinct clinical entity with highly effective targeted treatment options. The gene discussed is EGFR; the disease is large cell neuroendocrine carcinoma.