OBJECTIVES: Peripheral odontogenic fibroma (POF) is a relatively rare odontogenic tumor of the gingiva. Although its histological differential diagnosis from fibrous epulis (FE) is important, no study has reported the differences in their expression of immunohistochemical markers. Here, we compared the expression of tumor markers that are frequently used for the differential diagnosis of fibroproliferative lesions between POF and FE. METHODS: Forty cases were selected, including 20 POF and 20 FE cases. CD34, B cell lymphoma (Bcl)-2, and Ki-67 were used as markers for immunohistochemical examination. The positive cell ratio was calculated, and Mann-Whitney U test was performed for statistical analysis. RESULTS: POF and FE were negative for CD34 expression but showed Bcl-2 and Ki-67 expression. The ratio of Bcl-2- and Ki-67-positive cells was significantly higher in POF than in FE (p < 0.001). CONCLUSIONS: POF is CD34 negative, and Bcl-2 and Ki-67 positive-cell ratio differs between POF and FE, suggesting that these proteins may serve as immunohistochemical markers for the differential diagnosis of POF.