Primary amyloidosis isolated in the mediastinum is rarely encountered in thoracic surgery and few such cases have been reported. We present a case of primary isolated hilar amyloidosis of the mediastinum to illustrate the difficulties in differentiating this disorder preoperatively from central bronchial carcinoma, carcinoid tumor, and mediastinal lymphoma. Usually, a definitive diagnosis can only be made by open biopsy during thoracoscopy or thoracotomy. In conclusion, amyloidosis should be considered in the differential diagnosis of patients when calcifications are found, bearing in mind that radiologic findings are inconclusive and transbronchial biopsy can be negative.