Rationale. The receptor for advanced glycation end products (RAGE) engages a number of ligands implicated in inflammatory processes. RAGE coding gene maps to the 6p21.32 region, close to DRB1 and BTNL2, two genes associated with sarcoidosis. Objectives. Investigating a possible implication of RAGE in sarcoid granulomas. Methods. RAGE and major ligands (CML, S100A12 and S100B) expression was investigated by immunostaining of 99 paraffin-embedded biopsies of sarcoid tissues, and expression patterns determined. Among 3 RAGE gene SNPs investigated, the -374 T/A one was selected, characterized in terms of transcriptional effect (immunocytochemistry and real-time PCR), and its frequency was determined in DNA extracted from biopsies. Measurements and results. RAGE , CML, S100A12, and S100B immunoreactivity was observed in all sarcoid granulomas, although at different intensity. Degree of RAGE expression significantly correlated with degree of S100A12 expression. The -374 TT/AT genotypes, associated with higher RAGE transcriptional activity, were more frequent in the sarcoidosis biopsy group than in controls, and the association was confirmed in a second, independent series of 101 sarcoidosis patients. Conclusions. We showed the association of RAGE and its ligands with sarcoidosis, and suggest that an intrinsic genetic factor could be in part involved in its expression. In Italian patients, the -374 T/A polymorphism seems to be significantly associated with this disease. (Word count : 212)