Objective: Breast cancer remains one of the most common malignancies affect- ing women. In breast cancer, axillary lymph node (ALN) involvement is a useful clinical parameter for decision-making. Although ALN dissection is associated with upper extremity lymphoedema and other morbidities, the presence of ALN metastasis is the most important prognostic factor predicting breast can- cer patient survival. The prediction of ALN metastasis by evaluating expression of tumor-related proteins of primary breast cancer is potentially a promising approach because the primary tumor is readily assessed. Materials and Methods: Proteomic analysis has become an effective tool in breast cancer research. In this preliminary study, we aimed to examine the changes in protein expression patterns between the primary tumor and its axillary lymph node (ALN) metastasis of breast cancer. A robust and highly re- liable proteomics approach that is based on two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and spot image analysis was used. Results: In the light of our image analysis, we hypothesized that proteomics could predict ALN metastasis by pinpointing the alterations in protein profiles of primary breast cancer and axillary lymph node tissues. Results obtained from analysis of 2DE images revealed the presence of 24 conserved protein spots between primary breast cancer and its axiliary lymph node tissue. Conclusion: These candidate proteins may provide clues to the molecular mechanism of cancer spread into the lymphatic tissue and may allow early detection of this devastating disease.