We presented a middle-aged woman with nonspecific signs and symptoms, including dyspnea, lower limb edema, and elevated jugular venous pressure. Among these, the skin changes including nail changes, macroglossia and periorbital rash were the most important clues to suspect primary amyloidosis. Paraclinical studies were anemia, proteinuria and restricted cardiomyopathy. Abdominal fat pad biopsy is usually the first step to confirm the amyloidosis. However, despite the negative histologic result of fat-pad biopsy, we performed duodenal biopsy that confirmed amyloidosis. This case report demonstrates the important value of duodenal tissue in order to conform the diagnosis of amyloidosis.