The present report illustrates efficacy of rituximab (RTX) in granulomatosis with polyangiitis (GPA) with severe lung involvement. Female patient, 45 years old, was ill since March 2016, her disease manifested at the onset with fever, recurrent epistaxis, otitis media, mastoiditis, conjunctivitis and arthritis. Thoracic CT scan showed multiple decaying pulmonary infiltrates. The presence of PR3-ANCA confirmed the diagnosis of GPA. Induction therapy included high doses of glucocorticoids, cyclophosphamide (total dose 4 g), with following azathioprine and mycophenolate mofetil. Lung disease continued to progress with emerging extensive infiltrates and forming a giant cavity with air-fluid level in the right lung. Further treatment included antibiotics followed by surgical draining of lung cavity in December 2018. Fever, necrotic rhinitis and otitis persisted despite treatment, lab findings included red blood cells in the urine, C-reactive protein 90 g/l, thrombocytosis 740×109 /l, anemia (Hb 80 g/l). RTX 2 g and intravenous immunoglobulin were initiated in December 2018, a second course of RTX (0.5 g) was administered 4 months later. Patient’s condition was gradually improving, CT scan at 6 months after RTX treatment showed fibrous tissue in the area of former cavity. One year later, total RTX dose was 3.5 g, further regression of changes and GPA remission were achieved. There were no adverse reactions. Anti-B cell therapy with RTX is a safe and highly effective option in GPA patients with severe destructive lung disease, potentially curative even in cases of giant pulmonary cavities.