We present a 69-year-old male patient with the macroglossia, dysphagia and generalized edema. He was seen previously by other physicians and diagnosed as hypothyroidism. With thyroid stimulating hormone in normal range, tongue biopsy revealed primary systemic amyloidosis. Amyloidosis is the most common cause of macroglossia. Primary systemic amyloidosis should be suspected when laboratory does not support hypothyroidism especially if the enlarged tongue is firm and additional findings are present.