Are you treating extrapulmonary neuroendocrine carcinomas based on where they start—or what they actually are?In this faculty follow-up to their i3 Health activity (Clinical Challenges in Extrapulmonary NEC: Expert Insights on Diagnosis, Treatment, and Emerging Targets), Andrew Hendifar, MD, and Danielle Hutchings, MD (Cedars-Sinai Medical Center), unpack why treating these rare, aggressive tumors according to site of origin rather than tumor lineage can compromise outcomes. They clarify crucial pathologic distinctions between well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs) while emphasizing the essential role of multidisciplinary collaboration in precision care.The experts also explore the novel therapeutic landscape of delta-like ligand 3 (DLL3)–targeted therapies, highlighting the promise of DLL3 T-cell engagers in extrapulmonary disease. They address ongoing diagnostic hurdles—such as standardized immunohistochemistry (IHC) expression thresholds and expanding send-out testing access—while sharing key insights on emerging clinical trials evaluating T-cell engager monotherapies and chemo-immunotherapy combinations.Claim your CME credit: bit.ly/488fPhKDownload and review the companion Clinical Challenges in Extrapulmonary NEC Slide Deck: bit.ly/4w2Pni3