Purpose: rasgene product, p21Ras,was found to be overexpressed inhuman tumors.However, the subtypes of overexpressed p21Ras and mutation status are still unknownwhich limits the development of therapeutic antibodies targeting p21Ras.This study aims to investigatethe mutation status of rasgenes in breast cancers overexpressedp21Ras to real whetheror not wildtype p21Ras could be target for breast cancer therapy.Method: The expression of total p21Ras was examined immunohistochemically in normal breast tissue, usual ductal hyperplasia(UDH), atypical ductal hyperplasia(ADH), ductal carcinom in situ(DCIS) and invasive carcinoma (IC)by monoclonal antibody (Mab) KGH-R1which could react with three types of p21Ras.Then,the expression of p21Ras subtypesin breast cancerswas examined by specific Mab for each p21Ras subtypes.Mutation status of ras genes of p21Ras-overexpressed breast cancer were detected by DNA sequencing.Results: There were almost no p21Ras expression in normal breast tissue, but high level of expression in breast cancers, with generally significant increasingfrom UDH to ADH, DCIS and IC.The expression of K-p21Ras subtype was detected inall breast cancer, however, no N-p21Ras expression was found in all breast cancer, and only 4.2% of breast cancersdemonstrated H-p21Ras expression.Exon mutations were notdetected in three ras genes in all breast cancerswhich overexpressed p21Ras.Conclusions:The overexpression of wildtype p21Rasrather than mutantp21Ras plays a prominent role in the development of breast cancer, and wildtype p21Ras is a promising target for breast cancer therapy.