Abstract Our group has recently demonstrated the overexpression of the UbcH10 gene in undifferentiated thyroid carcinomas. Subsequently, a clear correlation between UbcH10 overexpression and a reduced survival in ovarian carcinoma patients has been described indicating UbcH10 as a valid prognostic marker in this neoplastic disease. Here we have extended the analysis of the UbcH10 expression to neoplastic breast diseases. We demonstrated, by tissue micro-arrays immunohistochemical studies, a significant difference ( p = 0.0001) in the mean percentage of UbcH10 stained cells between benign (0.22%) and malignant (11.01%) neoplastic lesions. High UbcH10 expression was associated with intense Ki-67 staining ( p = 0.015) and ErbB2 positivity ( p = 0.092). The suppression of the ErbB2 expression in breast carcinoma cell lines induces a reduction of UbcH10 level. Consistently, the inhibition of breast carcinoma cell growth was achieved following the block of UbcH10 protein synthesis by RNA interference. Therefore, these results suggest the perspective of a therapy of aggressive breast carcinomas based on the suppression of the UbcH10 function.