Neurofibromatosis type 1 is a common neurocutaneous syndrome, caused by an alteration of the NF-1 gene, which is a tumor suppressor. It has been reported to be associated with different types of benign and malignant tumors but its association to systemic diseases is uncommon and has not been reported previously to be associated with vasculitis particularly granulomatosis with polyangiitis (GPA). We report a case of a 17-year-old male patient, who, during his follow-up for neurofibromatosis type 1, in our outpatient consultation; we objectified hypereosinophilia at 1700 eosinophils/μl without a history of asthma or atopy. He reported a nasal obstruction with epistaxis and no rhinorrhea or pruritus. Physical examination revealed afebrile patient with the lesions of his neurofibromatosis type 1 without cutaneous rash or urticaria. Rhinoscopy didn't show any lesion. Laboratory tests revealed a normal renal function, negative 24-hour urine protein, and no biological inflammatory syndrome. Immunological tests noted positives cytoplasmic antineutrophil cytoplasmic antibodies, and a slight increase in antinuclear antibodies at 1/180. Extensive infectious research was negative. Computed tomography (CT) of the sinuses revealed a non-obstructive nasal septum deviation with anatomical variations, and a chest scan showed multiple bilateral pulmonary nodules and micronodules. After ruling out the other etiologies, we retained the diagnosis of granulomatosis with polyangiitis according to American College of Rheumatology (ACR) criteria 1990 and we could start early the treatment. To our knowledge, the association between Neurofibromatosis type 1 and vasculitis, particularly GPA, has not been reported previously, which makes our case original and confirms the utility of an extensive lesion assessment during the follow-up.