Reduced Axin expression has been associated with an aggressive behavior in lung and esophageal squamous cell carcinomas. Its role in breast cancer has not been defined. The aim of our study was to investigate the expression pattern of Axin protein in invasive breast carcinomas, in relation to the behavior and prognosis of the disease. Immunohistochemistry was performed for the detection of Axin expression in 232 breast cancer tissues. Univariate and multivariate statistical analyses were used to assess the relation of Axin expression with classic clinicopathological parameters, patients' survival and various biologic markers Human Epidermal Factor-2 (HER-2), Ki-67, topoIIα, glycogen synthase kinase-3β (GSK-3β)]. Preserved cytoplasmic Axin expression was positively correlated to lymph node invasion, HER-2 and GSK-3β and inversely to Ki-67 and topoIIα. Nuclear Axin was positively associated with tumor size. Stromal Axin showed a parallel association with lymph node status and HER-2. In the subgroup of lobular breast carcinomas, preserved Axin was found to exert an unfavorable impact on patients' overall survival. Our findings indicate, for the first time, that in invasive breast cancer preserved Axin expression is associated with a more aggressive phenotype and that in the discrete subtype of lobular breast carcinomas Axin negatively influences patients' overall survival.