Multilocular cystic renal neoplasm of low malignant potential (MCRNLMP) and multicystic renal cell carcinoma (MCRCC) are morphologically indistinguishable. MCRNLMP is a tumor composed entirely of numerous cysts, the septa of which contain individual or groups of clear cells without expansile growth. However, unlike MCRCC, neither recurrence nor metastasis has been reported in MCRNLMP. The aim of this study was to identify significant differential pathological characteristics in resected specimens from patients diagnosed with MCRNLMP (n=13) and MCRCC (n=17) using immunohistochemistry of 25 tissue markers. Staining interpretation was performed semi-quantitatively using the H-score (0-300) or intensity score (0-3), and differences between groups were evaluated using the Fisher exact and Wilcoxon rank-sum tests. During a median follow-up of 66.2 months (1-141.9 months), there was only one case of MCRCC recurrence among all 30 patients, including 19 (63.3%) at stage pT1a, 8 (26.7%) at stage pT1b, and 3 (10.0%) patients at stage pT2. Tumor necrosis rate (0% vs. 52.9%) and median tumor size (3.2 cm vs. 4.1 cm) significantly differed between MCRNLMP and MCRCC samples. Among the 25 tissue markers, only HIF1a, PDGFRα, SMA, VEGFR1, VEGFR2, VEGFR3, CD10, CD31, CD34, CK7-tubule, TGAse-2, and Ki-67 showed significantly different expression between the groups. These tissue markers with differential expression between MCRNLMP and MCRCC can provide a clue to understanding their distinct pathophysiology.