Orbital venous pathologies encompass a broad range of entities including tumors, shunts, congenital anomalies, aneurysms, and obstructive lesions. Patients may present with a variety of clinical findings which may include a combination of tumefaction, vascular engorgement, orbital pulsation, and exophthalmos, depending on the relationship between the lesion and the vascular system. Clinical findings may be unreliable in excluding serious underlying disorders, and so an extensive clinical and radiologic evaluation is necessary. This article presents a rare case of spontaneous aseptic cavernous sinus-superior ophthalmic vein thrombosis in a woman on hormone replacement therapy, and illustrates the multidisciplinary approach in diagnosis and management. The literature on issues surrounding this case is reviewed.