OBJECTIVE To explore the relationship of high S-phase kinase associated protein 2 (Skp2) expression with the characteristics of breast cancer.METHODS Using a immunohistochemical method, Skp2 expression was detected and evaluated in 30 normal tissues, 30 atypical ductal hyperplasias (ADH), 30 ductal carcinomas in situ (DCIS) and 56 invasive carcinomas (including invasive specific carcinoma and invasive nonspecific carcinoma). The relationship between Skp2 expression and the characteristics of breast cancer was analyzed.RESULTS Skp2 expression varied among normal tissue, ADH, DCIS and invasive carcinomas (χ2=54.02, P＜0.005). The positive level of Skp2 expression in DCIS was higher than that of normal tissue (χ2=21.82, P＜0.005) and there was a significant difference in Skp2 between DCIS and ADH (χ2=5.08, P＜0.025) as well as between invasive carcinomas and DCIS (χ2=6.52, P＜0.01). The positive expression level of Skp2 in invasive carcinomas with positive lymph nodes was remarkably higher compared to those with negative lymph nodes. A significant difference in Skp2 expression was found between combined histological Grades Ⅰ and Ⅱ versus Grade Ⅲ of invasive carcinomas (χ2=6.66, P＜0.01).CONCLUSION High Skp2 expression may play an important role in carcinogenesis and biological behavior of breast cancer.