Abstract: Objective: To investigate the clinicopathological characteristics of amyloidosis in the oral and maxillofacial region and evaluate the value of oral tissue biopsy to the diagnosis of amyloidosis. Methods: The clinical data of 55 amyloidosis cases from May 2010 to December 2014 were retrospectively analyzed. Oral tissue biopsy was applied for all of the patients by the authors and was analyzed by HE staining, alkaline Congo red staining and immunohistochemical staining. All sections were examined by transmitted and polarized light microscopy. One kidney biopsy tissue was observed via transmitted electron microscopy (TEM). Results: 46 oral tissue biopsy (gingival, glossa, lip and gland) presented positive outcome of amyloidosis with the positive rate of 84%. The amyloidosis was characterized as pink amyloid protein deposition under the basement membrane and in the wall of blood vessles, and was presented brick-like red by alkaline Congo red staining. The TEM results showed that the amyloid protein appeared like irregular and uneven flocculent structure. Conclusion: The amyloidosis in the oral and maxillofacial region mainly manifests enlargement, solidness and ulceration of the tongue. Oral tissue biopsy can provide an important evidence for amyloidosis disease diagnosis.