A 44-year-old man suffered a Buschke-Loewenstein tumor that was treated by distal penectomy. Ultrastructurally, this tumor showed widened intercellular spaces, prominent microvilli, decreased numbers of and incompletely developed desmosomes, decreased tonofilaments, cytoplasmic dense bodies, enlarged nucleoli and annular nuclear bodies. These ultrastructural features are quite similar to those of squamous carcinoma but are dissimilar to those of condyloma acuminatum and, to a lesser extent, verrucous carcinoma. These data suggest that electron microscopy may be useful in differentiating the neoplastic Buschke-Loewenstein tumor from large condyloma acuminatum.