Objective: To describe the chronology and the extent of orbital involvement in a case of granulomatosis with polyangiitis. Methods: Descriptive case report and literature review. Results: A 45-year-old patient, formerly diagnosed with granulomatosis with polyangiitis due to otorhinolaryngologic manifestations, pulmonary lesions, renal impairment, left knee arthritis and high blood levels of antineutrophil cytoplasmic antibodies, addressed the Ophthalmology Department in November 2020, having the following complaints: left eye mild retro-orbital discomfort, proptosis and epiphora. On examination, Snellen’s best corrected visual acuity was 6/ 6 in both eyes. The anterior segment of the left eye displayed significant changes: proptosis, upper lid swelling, ptosis, slightly decreased ocular motility, mild conjunctival hyperemia and chemosis, thinning of sclera in the upper quadrant and mild posterior subcapsular cataract. Left eye funduscopy revealed a slightly elevated optic disc, with indistinct margins in the nasal quadrant. Spectral-domain optical coherence tomography (OCT) of the optic nerve confirmed the clinical findings, illustrating an increase in the retinal nerve fiber layers thickness in the nasal quadrant, with no corresponding visual field defect. The orbit magnetic resonance imaging (MRI) unveiled an intraconal mass surrounding the optic nerve on its entire intra-orbital path, confirming the diagnosis of left orbital granuloma. Conclusion: Considering the relapsing disease and the orbital involvement, the patient is currently a candidate for rituximab, a monoclonal antibody against CD20. Abbreviations: AAV = ANCA associated vasculitides, ANCA = antineutrophil cytoplasmic antibody, AOM = acute otitis media, BCVA = best corrected visual acuity, CRP = C-reactive protein, CT = computerized tomography, EGPA = eosinophilic granulomatosis with polyangiitis, ENT = otorhinolaryngology/ ear-nose-throat, ESR = erythrocyte sedimentation rate, GPA = granulomatosis with polyangiitis, LE = left eye, MPA = microscopic polyangiitis, MRI = magnetic resonance imaging, OCT = optical coherence tomography, RE = right eye, RNFL = retinal nerve fiber layers, TNF = tumor necrosis factor, WG = Wegener’s granulomatosis