Epithelial ingrowth is a major complication of penetrating trauma or intraocular surgery. The present study was undertaken to analyze the clinical and histopathologic findings in a large series of consecutive patients. All cases of epithelial ingrowth on file in the Eye Pathology Laboratory of the Wilmer Ophthalmological Institute, Johns Hopkins Hospital, were included. Histopathologic slides of 207 consecutive cases of epithelial ingrowth were reviewed and, where necessary, additional sectioning and staining was performed. Transmission electron microscopy was performed in 15 cases and immunohistochemistry, in 28 cases. The histopathologic specimens included globes (46), corneal buttons (64), iris tissue (87), and block excisions (7). The causes of epithelial ingrowth were penetrating trauma (48), cataract surgery (123), keratoplasty (21), and others (15). There was a wide spectrum of presenting signs and symptoms, most frequently glaucoma (35), fistula (34), retrocorneal membrane (31), "uveitis" (29), iris cyst formation (28), pain (25), bullous keratopathy (20), and corneal graft failure (19). Glaucoma was present in 43.1% of eyes and fistula and/or wound dehiscence was present in 29 eyes. Epithelial ingrowth was cystic in 40 cases and diffuse in 167 and was not suspected prior to histopathologic examination in 36% of cases. Histologically a multilayer of surface epithelium was present on intraocular surfaces such as the cornea, iris, chamber angle, ciliary body, lens capsule, and Bruch's membrane. Epithelial ingrowth may present with a wide variety of often uncharacteristic signs and symptoms and should always be included in the differential diagnosis of unusual posttraumatic or postoperative findings.