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9% of poorly-differentiated NECs (G3 NEC), highlights DLL3 expression as a marker of G3 NECs (p = 0.007). DLL3 expression was correlated with RB1-loss (p less then 0.001), negative 68 Ga-PET/CT scan (p = 0.001), and an unfavorable clinical outcome, with important implications for treatment response and patient's follow-up. Median progression-free survival (PFS) and overall survival (OS) were 22.7 months (95% CI 6.1-68.8) and 68.8 months (95% CI 26.0-78.1), respectively, in patients with DLL3-negative tumor compared with 5.2 months (95% CI