BACKGROUND Hypoproteinemia is caused by a decrease in protein level in the blood. This report describes 2 cases of hypoproteinemia associated with a gigantic odontogenic tumor. CASE REPORT Case 1, a 65-year-old man, visited our hospital with the chief concern of swelling in the right mandible, approximately 100 mm in diameter, and ameloblastoma was diagnosed. Abscess drainage was observed in the fistula of the tumors. Total protein and albumin levels were low before surgery. Hemimandibulectomy was performed under general anesthesia. The final pathological diagnosis based on the specimen was ameloblastic carcinoma. After surgery, the total protein and albumin levels improved and remained stable 6 months after the operation. At 21 months after surgery, there were no signs of recurrence. Case 2, a 60-year-old woman, visited our hospital with a chief concern of swelling in the left mandible, approximately 100 mm in diameter, and ameloblastoma was diagnosed. Abscess drainage was observed in the fistula of the tumors. The patient had a history of hypoproteinemia; preoperative levels of total protein and albumin were low, and edema of the body was observed before surgery. Hemimandibulectomy was performed under general anesthesia. The final pathological diagnosis based on the specimen was ameloblastoma. After surgery, the total protein and albumin levels improved, and remained stable 6 weeks after surgery. There were no signs of recurrence 9 months after surgery. CONCLUSIONS These 2 cases indicate the possibility that hypoproteinemia can be caused by plasma leakage from fistulas associated with gigantic odontogenic tumors.