A 54-year-old female presented with multiple episodes of emesis, intractable headaches, worsening balance, and slowly progressive right facial weakness. Imaging demonstrated a 3-cm mass in the left internal capsule and corona radiata region with associated edema, mass effect, and midline shift concerning for high-grade glioma, lymphoma, or brain metastasis. Stereotactic biopsy of the mass was consistent with amyloid deposition. Systemic workup for amyloidosis was negative, and the mass was thought to represent a focal tumor-like deposit of amyloid, also referred to as “amyloidoma.” In the absence of systemic disease, therapy, which can include surgery or radiotherapy, can be directed at the local process. The location of the patient's lesion was not amenable to resection; therefore, she was treated with fractionated radiotherapy of 30.6 Gy at 1.8 Gy per fraction. Serial brain MRI demonstrated stability 18 months out from therapy. To the authors' knowledge, this is the first documented case of focal fractionated radiotherapy for CNS amyloidoma. The authors concluded that radiotherapy can prevent further progression of amyloidomas in anatomical locations that prohibit resection.