Pulmonary sclerosing hemangioma (PSH) is relatively rare and is usually considered a benign tumor because of its slow growth and solitary characteristics. However, several cases with lymph node metastasis have been reported, and its pathogenesis has not been fully elucidated. Three sets of PSH specimens from the Korea Lung Tissue Bank, obtained with IRB approval, were analyzed through the construction of an oligo-microarray that contained about 32,000 genes. The resulting data were confirmed by real-time RT-PCR. Protein expression levels were checked by performing immunohistochemistry (IHC) and immunoblot analysis. In the 3 specimens of PSH tissues, 72 of the 32,000 genes were commonly found up-regulated and 290 were commonly found down-regulated as compared to non-tumor tissues from each patient. Paraffin-embedded tissues from 11 cases were used to confirm the expression of matrix metalloproteinase 9 (MMP-9) and tubulin-alpha proteins in the non-tumor and PSH tissues via IHC. In addition, the upregulation of protein expression was confirmed by immunoblot analysis. As expected, in all cases MMP-9 and tubulin-alpha were expressed at significantly higher levels in the PSH than in the non-tumor tissues. This is the first report on a study of the whole genome of PSH. Increased expression of MMP-9 could induce the metastatic ability of PSH and tubulin-alpha might be responsible for the sclerotic character of this disease. The results of this study will be useful in helping to understand and effectively manage patients suffering from PSH.