CD44v6 contributes to apoptosis resistance and metastasis via upregulated activity of the PI3K/AKT pathway. The purpose of this study was to investigate the expression patterns and predictive value of phosphorylated AKT (pAKT) and CD44v6 in breast cancer tissues.Expression of pAkt and CD44v6 protein was detected using immunohistochemistry in breast cancer tissues and lymph node tissues in 98 patients. The correlation between the expression of pAkt, CD44v6 and other disease-related characteristics was investigated. The prognostic value of pAKT and CD44v6 overexpression for overall survival (OS) and disease free survival (DFS) was determined.37 cases (37.8%) were observed as positive for pAkt expression, and 38 cases (38.8%) for CD44V6 overexpression. Staining was positive for pAKT in 20 of 38 (52.6%) CD44v6(+) and 17 of 60 (28.3%) CD44v6(-) (P = 0.016). A progressively increased trend of CD44v6 overexpression was observed from node(-) primary breast cancer tissues to node(+) primary cancer tissues to node(+) lymph tissues (P = 0.000). In univariate analysis lymph node status, pAKT and CD44V6 were significantly associated with a decreased OS and DFS. Multivariate analysis revealed that CD44v6 status was associated with a reduced OS (P = 0.003), and pAKT and CD44v6 with a shorter DFS (P = 0.012 and 0.016, respectively).Our data suggested that there had an intensive relationship between pAKT and CD44v6 expression in breast cancer tissues. The overexpression of CD44v6 was an independent prognostic marker for predicting OS and DFS of breast cancer patients.