Background It is widely recognized that the diagnosis of parathyroid carcinoma (PC) is often difficult because of the overlap of characteristics between malignant and benign parathyroid tumors,especially at an early stage.Our study aimed to investigate the differential expression of Ki-67,galectin-3,fragile histidine triad (FHIT) gene,and paraflbromin in PC,parathyroid adenoma (PA),parathyroid hyperplasia (PH),and normal parathyroid (NP) tissues; then to assess these expression values for use in differential diagnosis of malignant and benign parathyroid tumors.Methods Data of 15 cases with PC,19 PAs,and 8 PHs were retrospectively analyzed for their clinical characteristics.The expression of Ki-67,galectin-3,FHIT,and paraflbromin were detected via immunohistochemistry in the above-mentioned specimens and 6 NPs as control.Results Complete loss of parafibromin expression was seen in 9 of 15 (60％) carcinomas,and all normal parathyroid tissues and parathyroid benign tumors stained positive for parafibromin except for one (4％) adenoma.Galectin-3 staining was positive in 11 of 15 (73％) carcinomas,5 of 19 (26％) adenomas,1 of 8 (12％) hyperplasias,and 0 of 6 normal tissues.The Ki-67 proliferative index was high in 4 of 15 (27％) carcinomas,1 of 19 (5％) adenomas,and none of the hyperplasia or normal tissues.FHIT expression did not differ appreciably among the tumor types.The combination of overexpression of galectin-3 or loss of parafibromin increased sensitivity for PC to 87％,while the specificity of both positive galectin-3 and positive Ki-67 could reach 100％.Conclusions These data suggested that loss of parafibromin and overexpression of galectin-3 and Ki-67 might help to distinguish parathyroid carcinoma from other parathyroid tumors.And the combination of two or three of these markers might produce better sensitivity and/or specificity for the diagnosis of parathyroid carcinoma.