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 im- munoreactions 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 (χ2 value was 1.371 and 3.352, respectively. P > 0.05). In contrast, there was a significant difference of vimentin between them (χ2 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, SP-B, EMA, vimentin and pancytokeratin may favor the diagnosis and differential diagnosis of PSH. Objective: To investigate the histogenesis and differential diagnosis of pulmonary sclerosing hemangioma (PSH). Methods: Thyroid transcription factor-1 (TTF-1), surfactant proteins A, B ), vimentin, pancytokeratin, cytokeratin7 (CK7), CK5 / 6, calretinin, S- 100, neurospecific enolase (NSE), synaptophysin (Syn), chromogranin A (CgA), CD34, ) 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 im- munoreactions with S- There were no significant differences between TTF-1 and EMA expression between these two cells (χ2 value was 1.371 and 3.352, respectively. P> 0.05). In contrast, there was A significant difference of vimentin between them (χ2 value was 17.720, P <0.001). Electron microcopy observation showed that ultrastructure may not differ from each other sometime. 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, SP-B, EMA, vimentin and pancytokeratin m ayfavor the diagnosis and differential diagnosis of PSH.