Introduction: To study the ultra-structural changes in the diseased corneal cells by histopathology, electron microscopy, and immunohistochemistry using conventional antisera and monoclonal antibodies with the ultimate goal of justifying pre-treatment and post-treatment advice and, if necessary, modifying the post-operative treatment for improved graft survival.Methods: Thirty cases registered for penetrating keratoplasty were worked up for routine systemic and ophthalmic criteria. A full-thickness diseased cornea was subjected to histopathology after suitable staining and fixation, including electron microscopic and immunohistochemical studies where possible.Results: The ages ranged from four to 60 years. The majority (26%) were in the age group of 31-40 years. The most frequent causes of corneal pathology that underwent keratoplasty include post-traumatic corneal scarring (40%), followed by pseudophakic bullous keratopathy (16.7%). In almost all cases, the histopathology confirmed the existing clinical diagnosis. Histopathology helped to confirm one doubtful case of Fuchs’ dystrophy and to contradict one clinical diagnosis of pseudophakic bullous keratopathy, which turned out to be epithelization of the anterior chamber.Conclusion: The results underline the significance of the histopathological study of these corneal conditions to increase the post-surgical survival of the corneal graft.