Follicular adenocarcinoma of the thyroid sometimes displays distant metastasis in spite of its low histological grade of malignancy. We have studied whether distant metastasis can be detected by the presence of blood vessel invasion. We have also examined the problem from the viewpoint of cell-to-cell conjugation. This study examined 160 cases of follicular adenocarcinoma of the thyroid. Histological specimens were made by sectioning tumors at their largest diameter. Blood vessel endothelia were specifically stained immunohistochemically with factor VIII-related antigen and Ulex europeaus agglutinin I (UEA-1). Then, the presence of blood vessel invasion was examined in detail. Furthermore, the conjugation of lectin-derived wheat germ agglutinin (WGA) to tumor cells was examined. Conjugation of tumor cells was also examined using sialic acid as a marker. Blood vessel invasion was recognized in 95 (59.4%) of 160 cases. Distant metastases were identified in 25 cases (15.6%) in which blood vessel invasion was also found. Relative to the group without distant metastases, the group with distant metastases showed not only a significantly higher sialic acid content but also higher levels of WGA-binding protein in the tissues. The risk of distant metastasis in patients with follicular adenocarcinoma of the thyroid appears to be related both to the extent and to the frequency of blood vessel invasion. Furthermore, assessment of the conjugation of cells appears to have predictive value for occurrence of distant metastases.