Podoplanin/aggrus is increased in tumors and its expression was associated with tumor malignancy. Podoplanin on cancer cells serves as a platelet-aggregating factor, which is associated with the metastatic potential. However, regulators of podoplanin remain to be determined. Transforming growth factor-beta (TGF-beta) regulates many physiological events, including tumorigenesis. Here, we found that TGF-beta induced podoplanin in human fibrosarcoma HT1080 cells and enhanced the platelet-aggregating-ability of HT1080. TGF-beta type I receptor inhibitor (SB431542) and short hairpin RNAs for Smad4 inhibited the podoplanin induction by TGF-beta. These results suggest that TGF-beta is a physiological regulator of podoplanin in tumor cells.