Background: Granulomatosis with polyangiitis (GPA) is a rare disease of unknown cause. The multitude of manifestations presents significant diagnostic challenges. This is a unique case of GPA with sinonasal, airway, skull base, petrous bones, vascular, and brain parenchyma involvement. Methods: We present a case of a 45-year-old female with a several day history of headache and left hearing loss. MRI brain demonstrated a large erosive enhancing soft process in the sinonasal cavity and nasopharynx. Results: She developed new ipsilateral rightward tongue deviation. A second MRI demonstrated disease progression. It showed posterior pharyngeal wall ulceration, involvement of the skull base foramina, petrous bones, and central bony skull erosion. It demonstrated right hemiglossal edema secondary to right hypoglossal nerve compression at the skull base. There was enhancing soft tissue partially encasing the left petrous internal carotid artery and more extensively encasing and narrowing bilateral intradural vertebral arteries with associated brainstem edema secondary to direct mass effect and new left occipital thromboembolic infarct. She underwent a nasopharyngeal biopsy which demonstrated acute inflammation on a background of GPA. Conclusions: There are no pathognomonic imaging characteristics for GPA. By recognizing the common and less-common imaging features, radiologists play a crucial role in both diagnosing and monitoring the disease activity.