Granulomatosis with polyangiitis (GPA) is a necrotizing granulomatous vasculitis occasionally affecting central nervous system (CNS), and GPA patients with initial CNS symptoms are even rarer, whose diagnosis is further confused by an absence of positive antineutrophil cytoplasmic antibody. The authors described the characteristics of antineutrophil cytoplasmic antibody -negative GPA with CNS onset in a patient and discussed on its management, which may contribute to future diagnosis and treatment of patients with similar conditions.