PURPOSE: A CXCR4/stroma derived factor-1alpha (SDF-1alpha, CXCL12) interaction is involved in many metastatic cancer mechanisms, including breast cancer. The primary objectives of this study were to investigate the correlation between CXCR4 and axillary lymph node metastasis and to clarify the interaction between CXCR4 in primary tumor cells and SDF-1alpha in metastatic lymph nodes. An analysis of the correlation between CXCR4, SDF-1alpha and clinicopathologic features was also performed. METHODS: Representative areas from 44 invasive ductal carcinomas were selected for construction of tissue microarrays using a 5 mm punch. Breast cancers (n=44), metastatic axillary lymph nodes (n=18) and non-metastatic axillary lymph nodes (n=26) were immunohistochemically stained for CXCR4, SDF-1alpha, estrogen receptor (ER), progesterone receptor (PR) and HER2. The parameters of age, tumor size, nuclear grade, histologic grade, lymph node status and pathologic node (pN) stage pN0 to pN3 were evaluated. RESULTS: CXCR4 expression was negatively correlated with increased age (p=0.005) and positively correlated with a large tumor size (p=0.043) and PR expression (p=0.027). CXCR4 expression was not correlated with metastatic lymph nodes (p=0.079) and SDF-1alpha expression in metastatic lymph nodes (p=0.062). However, CXCR4 nuclear positivity is correlated with lymph node metastasis (p=0.044). SDF-1alpha was not correlated with any clinicopathologic feature in a statistically significant manner. CONCLUSION: An evaluation of young age, large tumor size and PR expression helps predict lymph node metastasis and poor prognosis. Expression of CXCR4 nuclear positivity is correlated with a poor prognosis.