We report a distinctive lesion of the labium majus resected in 14 girls from 3.9 to 13.2 years of age. All presented with enlargement of 1 or occasionally both labia majora. Radiographic imaging and surgical exploration showed expansion of the labium majus without definable borders. Grossly, specimens consisted of fibro-fatty tissue from 2 to 8 cm in greatest dimension. Microscopic examination revealed the usual constituents of vulvar soft tissue, with expansion of the fibrous component. Sparsely to moderately cellular interconnected bands encircled lobules of fat, blood vessels, and nerves. The bands consisted of plump and occasionally stellate or round fibroblasts immersed in an abundant pale myxoid matrix containing thin collagen fibers. These fibrous bands merged with thinner denser fibrous septa simlar to those seen in the vulva from age-matched controls. Elastic stains showed variably abundant thin parallel elastic fibers. Fibroblasts were immunohistochemically positive for estrogen and progesterone receptors. Electron microscopy showed fibroblasts with dilated rough endoplasmic reticulum cisternae and prominent nuclear fibrous laminae; extracellular matrix contained precollagen, collagen, elastic fibers, and numerous proteoglycan granules. Cytogenetic analysis of 3 lesions revealed a normal karyotype. Recurrence was observed in 7 (50%) patients, and regression was observed in 1 whose recurrence was not reexcised. Over an 11-year period at Children's Hospital (Boston, MA), these lesions represented 22% of all pediatric vulvar soft tissue masses and 3% of all vulvar lesions biopsied. We conclude that "childhood asymmetric labium majus enlargement" is a distinctive clinicopathologic entity of pre- and early puberty. Recognition of this fairly common lesion is important, since it may clinically, radiographically, and histologically mimic an infiltrative neoplasm. Its occurrence at an age roughly coincident with the time of breast budding, capacity for spontaneous regression, histologic architecture and composition of elements native to the vulva, expression of hormone receptors, and normal karyotype suggest that it is an asymmetric physiologic enlargement in response to hormonal surges of pre- and early puberty.