While data pertaining to comprehensive genomic sequencing in pancreatic NECs has traditionally been sparse, a number of recent series have demonstrated enrichment for alterations in TP53, RB1, APC, KRAS, BRAF18,19, copy number losses in ARID1A, ATM and ESR1, in addition to amplifications/gains in MYC and KDM5A19. The gene discussed is ESR1; the disease is pancreatic endocrine carcinoma.