It has been reported that both polygonal and cuboidal cells in pulmonary sclerosing hemangioma (PSH) are monoclonal in origin and represent a variable differentiation from a common progenitor cell. However, it remains unclear about the clonality of the entire PSH lesion composed of these two types of cells. Thus, we analyzed the clonality of 22 cases of PSH and the relationship between the entire PSH and two types of cells using laser microdissection and X-chromosomal inactivation mosaicism and polymorphism at the phosphoglycerate kinase (PGK) and androgen receptor (AR) loci in female somatic cells. The results demonstrated all 22 cases of PSH showed typical histopathologic characteristics, including characteristic round or polygonal cells within the stroma and surface cuboidal cells lining the papillary projections or cystic spaces. The rates of polymorphism were 31.8% (7/22) and 86.3% (19/22) for the PGK and AR gene, respectively. After digestion by Hpa II or Hha I, one of two PCR amplification bands disappeared from all the samples, while the other band was retained, indicating neoplastic characteristics. Thus, we concluded that the entire PSH lesion, polygonal and cuboidal cells were neoplastic hyperplasia and originated from a common progenitor cell.