Objective To investigate lymphangiogenesis, lymphovascular invasion (LVI) and the expression of vascular endothelial growth factor D (VEGF-D) and their correlations in different regions of human breast cancer, and to evaluate their associations with axillary lymph node metastasis. Methods Tissue samples of primary tumors from 79 patients undergoing curative surgical resections for breast cancer were divided into four regions: tumor region, peritumoral region, nearertumor region and farthertumor region. Samples from the different regious were immunohistochemically examined for D2-40 and VEGF-D to evaluate lymphatic vessel density (LVD), LVI and VEGF-D expression in different regions. Results LVD in the peritumoral region was highest 20.25±2.03, and the positive rates of VEGF-D expression and LVI in tumor region were also highest (87.34% and 63.29%, respectively). In the tumor region, there was no significant correlation (P>0.05) between LVD and VEGF-D expression, between LVD and LVI, and between VEGF-D expression and LVI; however, there were significantly positive linear correlations (P<0.05) in other regions. Axillary lymph node metastasis significantly correlated with LVD in the peritumoral region, and significantly correlated with VEGF-D expression and LVI in the peritumoral and nearertumor regions (EM>P/EM><0.05). Conclusion The expression of VEGF-D might promote lymphangiogenesis and increase the chance of lymphovascular invasion in human breast cancer. The increase of LVD easily promotes LVI and axillary lymph node metastasis. The peritumoral and nearertumor regions may play more important roles in the study of lymphangiogenesis, lymphatic spread of breast cancer and in th