Chronic nodular prurigo (CNPG) is a multifactorial skin disease characterized by itchy papules and nodules, usually resistant to standard treatment and associated to markedly impaired quality of life.To describe dupilumab effectiveness and tolerability in treating adult patients with CNPG refractory to both topical and systemic therapies.Retrospective, multicenter study including adult patients affected by CNPG, who were treated with dupilumab for at least 16 weeks.Twenty-seven CNPG patients showed clinical improvement in terms of skin lesions, itch, sleeplessness, and quality of life. A consistent proportion (24/27, 88.9%) of patients had at least 16-week continuous treatment and achieved IGA 1 (11/24, 45.8%). An increased number of patients achieving at least 2-grade reduction in IGA score (19/24, 79.2%). Itch-Numeric Rating Scale (NRS) and sleeplessness-NRS values dropped from 8.9 to 2.7 and from 8.2 to 1.7, respectively (p values < 0.001), after 16-week therapy. Ten patients achieved 36 weeks of continuous treatment maintaining clinical efficacy.Major limitations include: lack of validated assessment tools at the time of initial data collection, limited cohort of treated patients, and short term observation period.Dupilumab was proven effective in reducing itch and improving CPNG skin lesions.