Background. Recalcitrant frontal sinusitis in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have a negative impact on quality of life due to frontal pain and a high risk of sinus occlusion, thus necessitating repeated courses of antibiotics, systemic corticosteroids, and multiple surgeries. Objective. The aim of this study was to investigate if the use of biologics can improve symptoms including facial pain and reduce use of rescue treatments in patients with severe uncontrolled CRSwNP and concomitant recurrent frontal sinusitis. Materials and Methods. This is a real-life, observational, no-profit case series. Between November 2022 and December 2023, we enrolled cohort of 10 patients with severe uncontrolled CRSwNP and concomitant recurrent frontal sinusitis associated to invalidating facial pain measured by MIDAS score and that were treated with dupilumab 300 mg every 2 week and followed for at least 12 months. Results. the mean MIDAS score decreased from 45.6±10.7 at baseline to 1.3±2.3 at 6 months (p<0.05). The same trend was observed for VAS craniofacial pain: from 7.3±1.6 at baseline to 1.2±1.5 at 6 months (p<0.05). The use of systemic corticosteroids and analgesics was significantly reduced. No patient needed oral corticosteroids during treatment with dupilumab (p<0.05), and the use of analgesics decreased from 9.6±3.1 mean brief cycles of NSAIDs at baseline to 0.6±1.3 at 1 year of follow-up (p<0.05). Discussion. Our results demonstrated that use of an anti-type-2 inflammatory pathway biologic can improve symptom control including recurrent craniofacial pain and reduce the need for rescue medical treatments in patients with severe uncontrolled CRSwNP and concomitant recurrent frontal sinusitis.