Benign fibrous histiocytoma of the skin or dermatofibroma (DF) has been reg
arded as a fibrohistiocytic tumor. Whether DF is a neoplastic growth or a r
eactive process has not been settled. Since a neoplastic process is clonal
in nature, clonal analysis of DF was conducted to see if DF is a clonal dis
ease. Fresh specimens of 13 DFs and 2 hypertrophic scars obtained from fema
le patients were studied. The adjacent nonlesional skin tissues served as c
ontrols. The clonal analysis was based on the methylation pattern of the po
lymorphic X-chromosome linked androgen-receptor gene (HUMARA). Eight DFs an
d 1 hypertrophic scar were heterozygous at the androgen receptor gene and c
ould be analyzed. All 8 informative DFs showed a significant reduction in o
ne of the allelic bands compared with the corresponding bands of the nonles
ional tissue after Hha I digestion. Therefore, DF is a clonal proliferative
disease. In contrast, 1 hypertrophic scar showed a polyclonal pattern of X
-chromosome inactivation. We conclude that DF is a clonal disease favoring
a neoplastic process.