Purpose The purpose of this study was to confirm the presence of specific patterns of epithelial response in corneal buttons from keratoconus patients. Methods This was a retrospective and descriptive study. 90 penetrating keratoplasty specimens obtained from patients diagnosed with keratoconus were evaluated using bright-field microscopy. Morphologically identifiable characteristics including epithelial cell density and epithelial thickness were analyzed on hematoxylin and eosin- (H&E-) and periodic acid of Schiff- (PAS-) stained slides. Results Three distinctive patterns of epithelial alteration of the central cornea were established. Pattern 3, in which the central epithelium was as thick as peripheral epithelium, was the commonest (44.4%), followed by the pattern 2, defined as central epithelium thinner than periphery epithelium (38.9%), and the uncommonest pattern was number 1, with central epithelium thicker than the periphery (16.7%). Conclusions Three distinctive histologic patterns that could potentially have a diagnostic and prognostic value in keratoconus patients were found.