Histologically, vulvar intraepithelial neoplasm (VIN) is a proliferative disorder of the female vulva. No single clinical characteristic or pathognomonic feature facilitates the diagnosis of VIN, and the agreement between different pathologists on the diagnoses varies significantly. In this study, we evaluate the immunohistochemical expression patterns of E-cadherin and β-catenin in 22 patients with VIN and 10 patients with non-neoplastic vulvar lesions. our results showed that membranous staining for E-cadherin and β-catenin was observed in squamous epithelial cells of all control non-neoplastic vulvar samples. Abnormal E-cadherin (17/19, 89.5%) and β-catenin (15/19, 78.9%) staining occurred more frequently in usual-type VIN than in non-neoplastic vulvar lesions (P=0.000 and P=0.000, respectively). However, in differentiated VIN, only 1 patient showed abnormal E-cadherin and β-catenin immunohistochemical expressions, which did not differ significantly. The abnormal expression of E-cadherin and β-catenin proteins might be useful in distinguishing VIN from non-neoplastic vulvar squamous epithelium lesions in problematic cases.