This study details the clinicopathologic and immunohistochemical features associated with 10 cases of a distinctive myointimal proliferation involving the corpus spongiosum of the glans penis. Patients ranged in age from 2 to 61 years old (mean age, 29 yrs) and presented with a mass that varied in size from 0.5 to 1.9 cm in greatest dimension. The process was said to be present from 4 days to more than 6 months before surgical intervention. In each case, microscopic examination revealed almost identical histology. There was a prominent, often occlusive, fibrointimal proliferation with plexiform architecture involving the vasculature of the corpus spongiosum. The proliferation consisted of stellate-shaped and spindled cells embedded in abundant fibromyxoid matrix. Occasional lesional cells had well-developed myoid characteristics with moderately abundant eosinophilic cytoplasm, blunt-ended nuclei, and juxtanuclear vacuoles. Foci with degenerative changes, including "ghost cell" morphology, were also present. The myointimal process was extensively immunoreactive for alpha-smooth muscle actin, muscle-specific actin (HHF-35), and calponin, but it was minimally reactive for the D33 and D-ER-11 desmin clones. In contrast, native vascular smooth muscle encompassing the proliferation was strongly immunoreactive for all five markers. The myointimal cells were nonreactive for CD34, S-100 protein, and keratin. Factor VIIIrAg, CD31, and CD34 highlighted intact endothelial cells lining suboccluded vessels, scattered capillaries that penetrated the proliferation, and the normal uninvolved vasculature. The examined specimens were punch, incisional, or excisional biopsies, and in each instance, the process microscopically extended to the tissue margin. Follow-up data are available for 8 cases (median follow-up interval, 5 yrs 8 mos): one incompletely excised lesion with 6 months follow-up is stable but persistent, one lesion with 10 years follow-up regressed spontaneously after a punch biopsy, and the remaining six lesions have not recurred. A differential diagnosis of myofibroma, late-stage intravascular (nodular) fasciitis, vascular leiomyoma, and plexiform fibrohistiocytic tumor is discussed.