Epithelial invasion after open globe injury is a rare complication. Wrong treatment (laser opening of the cyst) or no treatment can lead to painful blindness. Forty percent (25/62) of patients with block excision with epithelial downgrowth had a history of open globe injury. Four of them were female. Their mean age was 45 ±21 years. A tectonic keratoplasty with block excision was performed on 25 patients. Seven of them had simultaneously undergone cataract surgery. The mean extension of epithelial invasion was 3.0 ± 1.3 clock hours. Laser cystotomy was contraindicated. The diameter of the block excision was 8.2 ± 1.5 mm. Histological examination revealed diffuse epithelial invasion in three eyes and cystic epithelial downgrowth in 22 eyes. Mean pre‐ and post‐operative visual acuity (20/60) did not differ significantly. The intraocular pressure was 16 ± 7 mm Hg before and 14 ± 7 mm Hg after the surgery. Only one eye (4%) developed ocular hypotony after block excision. Epithelial invasion can become manifest many years after an open globe injury. En block excision for cystic epithelial downgrowth with an extension less than 150 degrees is the therapy of choice. Opening of the cyst by laser or surgically is not recommended: It can induce transformation of cystic into diffuse epithelial invasion, and the succeeding secondary glaucoma can be refractory to therapy and lead to blindness. Clin. Anat. 31:68–71, 2018. © 2017 Wiley Periodicals, Inc.