Objective： To investigate the histogenesis and differential diagnosis of pulmonary sclerosing hemangioma （PSH）. Methods： Thyroid transcription factor-1 （TTF-1）, surfactant proteins A, B （SP-A, SP-B）, epithelial membrane antigen （EMA）, vimentin, pancytokeratin, cytokeratin7 （CK7）, CK5/6, calretinin, S-100, neurospecific enolase （NSE）, synaptophysin （Syn）, chromogranin A （CgA）, CD34, factor-Ⅷ-related antigen （F-Ⅷ） and smooth muscle actin （SMA）in 55 patients with PSH were examined with immunohistochemistry, while samples from 19 patients were also observed by electron microscope. Follow-up information were reviewed. Results： Pathologically, PSH mainly consisted of both surface lining cuboidal cells and pale polygonal cells. Immunohistochemitry revealed that coexpression of TTF-1, EMA and vimentin in both cuboidal and polygonal cells was 94.5 % （52/55）, 90.5% （50/55） and 58.2% （32/55）, respectively. In cuboidal cells, the expression of SP-A and SP-B was 92.7% （51/55） and 81.8 % （45/55）, respectively. Whereas pancytokeratin and CK7 immunostained the cuboidal cells in all cases. The polygonal cells were difussed immunostained with Syn in 13 PSHs （24%） and NSE in 8 PSHs （15%）, while immunoreactions with S-100 and CgA were separated detected in 7 PSHs （13%）. There was no significant difference of TTF-1 and EMA expression between these two cells （χ^2 value was 1.371 and 3.352, respectively. P 〉 0.05）. In contrast, there was a significant difference of vimentin between them （χ^2 value was 17.720, P 〈 0.001）. Electron microcopy observation showed that ultrastructure may not differ from each other sometime. The follow-up was obtained for 49 cases ranged from 3 months to 14 years. 48 of them had no recurrence or metastasis except one case had recurrence. Conclusion： PSH may origin from the primitive respiratory epithelial. Polygonal and cuboidal cells are all parenchymal neoplasm cells. The concomitant examination of TTF-1, SPA,
