A 15-yr-old female Madagascar ground boa (Boa madagascariensis) presented with a history of anorexia, wheezing, and occasional open-mouth breathing. On oral examination, a firm, caseous mass was noted in the right caudoventral pharyngeal region, which was confirmed as a carcinoma on incisional biopsy. Advanced imaging (computed tomography and magnetic resonance imaging) was performed to evaluate local tumor invasion and to plan for palliative radiation therapy. However, following the second treatment (10 Gy), the mass had increased in size, and the snake was euthanatized. Radiation-associated vasculitis was noted within the soft tissues surrounding the mass and within muscles and the lung, which was verified on histopathology. The squamous cell carcinoma of the snake in this report was resistant to palliative radiation therapy.