Angiomyofibroblastoma (AMFB) of the genital region is a relatively recently described tumor of the superficial soft tissues with a marked preference for female patients. Three cases of AMFB were reviewed, two of which involved adult men. To further elucidate the pathologic features of AMFB, these three cases were compared with 10 cases of aggressive angiomyxoma (AA), a salient diagnostic alternative, and 28 cases of other myxoid tumors that may show morphologic similarities to these neoplasms. Conventional histologic and immunohistochemical features of AMFBs were compared with those of AA, myxoid leiomyoma, myxoid leiomyosarcoma, myxoid liposarcoma, myxoid malignant fibrous histiocytoma, myxoid neurofibroma, and myxoid malignant peripheral nerve sheath tumor. The ultrastructure of two of the three AMFBs also was analyzed. Genital AMFBs were circumscribed, partially myxoid proliferations that demonstrated considerable variation in cellular density. Neoplastic elements were bland cytologically and showed both fusiform and epithelioid profiles, with a tendency to concentrate around intralesional blood vessels. Mitotic activity and necrosis were absent, and the vessels assumed an arborizing configuration and were venule or capillary sized. In contrast, all other tumor types evaluated were infiltrative, cytologically atypical, or both. All AMFBs showed immunoreactivity for vimentin, desmin, actin, and estrogen receptor protein. These results were shared by most examples of AA and smooth muscle tumors as well, but were not seen in any other neoplasms in this study. Electron microscopic findings in cases of AMFB supported the presence of myofibroblastic differentiation in the tumor cells. These results indicate that conventional morphologic analysis is paramount in the recognition of genital AMFB but that immunohistology may be helpful in a limited context in excluding other differential diagnoses. They also support the conclusion that AMFB, AA, and superficial smooth muscle tumors have similar morphotypes and immunohistologic attributes regardless of their origin in men or women.