Epithelial cell proliferation is often observed in periapical lesions of endodontic origin. The mechanisms which stimulate the epithelial cell rests of Malassez to proliferate are not understood fully. Fifteen inflammatory periapical lesions (10 granulomas and five cysts) obtained from periapical surgery and six additional periapical lesions (four granulomas and two cysts) collected from extracted teeth were examined using immunohistochemical staining and 125I-EGF (epidermal growth factor) binding assay to detect the presence of epidermal growth factor receptor. The results indicated that the periapical lesions without epithelial cell proliferation had a weak immunoperoxidase staining or low specific binding of 125I-EGF. In contrast, the periapical lesions with epithelial cell proliferation and cyst formation exhibited a strong immunoperoxidase staining in the epithelial cells or high specific binding of 125I-EGF.