Background. Granuloma annulare (GA) and sarcoidosis are granulomatous inflammatory diseases that share similarities. Objective. To identify the histological and immunohistochemical (IHC) features of GA and sarcoidosis. Methods. A retrospective review of 36 patients with GA and 26 with sarcoidosis was performed. Results from hematoxylin and eosin (H&E) staining and IHC staining of MMP-9 and pSTAT1 within the skin lesions of GA and sarcoidosis were analyzed, and random forest was applied for developing a predictive model. Results. Significantly greater expressions of MMP-9 (especially in elastic fibers, EFs, P < 0.0001 ) and pSTAT1 ( P = 0.0003 ) were observed in lesion samples of GA versus sarcoidosis patients. In GA patients, MMP-9 was significantly upregulated in the interstitial type ( P = 0.0222 ), while staining of pSTAT1 was positively correlated with the area of mucinous collagen in palisading GA ( R = 0.5356 , P = 0.0484 ). In sarcoidosis patients, MMP-9 ( R = − 0.7127 , P = 0.0009 ) and pSTAT1 ( R = − 0.5604 , P = 0.0067 ) were found to show stronger expressions in lesions with less lymphocyte infiltration. The predictive model demonstrated an AUC of 0.9675. Conclusion. These results indicate that MMP-9 and pSTAT1 might exert roles in granulomatous inflammation in different modes, and the presence of more robust MMP-9 staining in EFs appears to be more suggestive of GA.