No studies have ever precisely investigated the mechanism of nodal metastasis based on the histological characteristics of tumor cells in lymph vessels and lymph nodes. The purpose of this study was to investigate whether the histological characteristics of tumor cells in lymph vessels and lymph nodes of 393 patients with invasive ductal carcinoma (IDC) were significantly associated with increased nodal metastasis compared with well known histological characteristics of their primary-invasive tumor cells. Multivariate analyses showed that having a single nodal metastasis was closely dependent on primary-invasive tumor size or distance of lymph vessel tumor emboli from the margin of the primary-invasive tumor (P < 0.05) and that having 2 or more nodal metastases was significantly associated with the histological characteristics of the nodal metastatic tumors independently of the size of the primary-invasive tumor, and the number of nodes with extra-nodal invasion (ENI) significantly increased the relative risk (RR) of 4 or more nodal metastases in IDCs </= 20 mm and > 20 to </= 50 mm in size (P < 0.05). In IDCs > 50 mm in size, number of lymph vessels invaded, severe fibrosis of the stroma of extra-nodal invasive tumors, and distance of ENI from the node significantly increased the RR of 10 or more nodal metastases in the multivariate analysis (P < 0.05). The results of this study strongly suggest that the histological characteristics of tumor cells in lymph nodes and lymph vessels play an important role in nodal metastasis in IDCs of the breast.