Galectin-9, a member of the beta-galactoside-binding animal lectin family, is involved in various cellular biological events, including aggregation and apoptosis, adhesion of cancer cells, and dendritic cell maturation. We recently reported the relationship between galectin-9 expression in tumor tissue and distant metastasis in breast cancer. Tumors in 42 of the 84 patients were galectin-9-positive, and tumors in 19 of the 21 patients with distant metastasis were galectin-9-negative, assessed by immunohistochemistry. The cumulative distant metastasis-free survival ratio for galectin-9-positive patients was better than for the galectin-9-negative group (p < 0.0001). Multivariate analysis revealed that galectin-9 status influenced distant metastasis independent of and much more than lymph node metastasis. MCF-7 subclones with a high level of galectin-9 expression formed tight clusters during proliferation in vitro, whereas a subclone (K10) with the lowest level of galectin-9 expression did not. However, K10 cells stably transfected with a galectin-9 expression vector aggregated in nude mice as well as in culture. Ectopic expression of galectin-9 also reduced MCF-7 cell adhesion to extracellular matrix proteins.