Myeloid sarcoma in a patient with myelodysplastic syndrome (MDS) manifesting as a non-healing tonsillar ulcer is an extremely rare occurrence. We report the case of a 57-year-old male smoker with a non-healing tonsillar ulcer who underwent tonsillectomy to rule out tonsillar carcinoma after failed antibiotic therapy. On postoperative day 2, he presented with a temperature of 40°C and white blood cell count of 34700/μL. Antibiotic therapy was begun; however, he died 1 day later due to pulmonary infection and septic shock. Though extremely rare, tonsillar involvement of MDS should be considered in the differential diagnosis of a non-healing tonsillar lesion. When definitive diagnosis requires a tissue sample, punch biopsy may be preferable to tonsillectomy in a patient who may be immunocompromised, and appropriate prophylactic antibiotics should be administered.