Stromal vascularity is thought to be a major factor involved in the progression of carcinoma. However, the crucial mechanisms of vascularization in the stroma are not well understood. Vascularity could be regulated by various cytokines produced by neoplastic or stromal cells in carcinoma. Thrombospondin (TSP) has an inhibitory role against vascularization in vitro, although the biological significance of TSP has not been characterized in vivo. We examined expression of TSP1 and TSP2 genes in 78 non-small cell lung cancers (NSCLCs) and 33 extraneoplastic lung tissue samples by reverse transcription-PCR. TSP1 expression was detected in 66.7% (52 of 78) of NSCLCs and in 69.7% (23 of 33) of extraneoplastic lung tissue specimens. TSP2 expression was seen in 48.7% (38 of 78) of NSCLCs, whereas 72.7% (24 of 33) of extraneoplastic lung tissue samples showed TSP2 gene expression. TSP2 expression was significantly decreased in NSCLC as compared with extraneoplastic lung tissue (chi2 test, P=0.019). Vascularity in the NSCLC was inversely correlated with TSP2 gene expression (Mann-Whitney U test, P=0.009). Patients with adenocarcinoma positive for TSP2 gene expression (22 of 49) showed significantly better prognosis than those without TSP2 (27 of 49; Cox-Mantel test, P=0.034). TSP1 expression showed no apparent correlation with these factors. These results suggested that TSP2 had an inhibitory role against vascularization and progression of NSCLC.