Elastofibroma is a rare fibrous lesion that most commonly occurs in periscapular soft tissues and is characterized by accumulated abnormal elastic fibers. Although the lesion is generally regarded as a reactive process, an unusual fibroblastic pseudotumor, or as a fibroelastic tumor-like lesion, its etiology remains largely unknown. Recent cytogenetic demonstrations of chromosomal instability and some recurrent or clonal chromosomal changes have raised the possibility that the lesion represents a neoplastic process. We analyzed 14 cases of elastofibroma to further explore, morphologically and genetically, the characteristics of its cellular composition. The interspersed spindle or stellate cells showed a fibroblast-like appearance and were almost consistently positive for vimentin and frequently positive for CD34 and lysozyme immunohistochemically. No spindle cells of myofibroblastic phenotype were recognized. To assess the clonality of the lesions in female patients, the X-linked polymorphic human androgen receptor gene assay was performed using formalin-fixed, paraffin-embedded tissues. A nonrandom inactivation of the androgen receptor gene was detected in two informative cases. Thus, these findings suggest that CD34-positive mesenchymal cells are an integral component of elastofibroma, which represents a clonal fibrous proliferation.