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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.