Purpose To determine the epithelial lineage of origin of surgically removed grafts after autologous cultivated oral mucosal epithelial transplantation (COMET). Design Retrospective comparative case series. Participants We studied 6 eyes from 5 patients with total corneal stem cell destruction; 3 eyes were from patients with Stevens–Johnson syndrome and 3 eyes had sustained chemical injury. Methods Autologous cultivated oral mucosal epithelial sheets on human amniotic membrane (AM) were transplanted onto the ocular surface. Regrafting (2 eyes) or penetrating keratoplasty (4 eyes) was performed after the initial transplantation procedure for further visual rehabilitation. Main Outcome Measures The excised grafts were subjected to clinical evaluation and to light, scanning, and transmission electron microscopic (EM) study and to immunohistochemical analysis. Results In clinically failed grafts, EM and immunohistochemical analysis disclosed only small areas where the original cultivated oral epithelial cells persisted. Neighboring conjunctival epithelial cells had apparently invaded a large portion of the corneal surface (keratin 3[−], Muc5ac[+]); there were many blood vessels and inflammatory cells. In clinically successful grafts, transplanted cultivated oral epithelial cells survived and had adapted well to the host corneal tissues (keratin 3[+], Muc5ac[−]); there was no infiltration by inflammatory cells, nor was there dissolution of the AM substrate. Conclusions We posit that the process of graft opacification after COMET is responsible for the loss of transplanted cultivated oral epithelial cells and that this is followed by conjunctival cell invasion onto the corneal surface. We confirmed that in clinically successfully grafted eyes, autologous cultivated oral epithelial cells survived on the corneal surface and maintained ocular surface integrity.