OBJECTIVE To evaluate patients with ocular surface squamous neoplasia (OSSN) on treatment with topical mitomycin C (MMC) with regard to changes in corneal thickness and endothelial count. METHODS Prospective, nonrandomized, interventional series. METHODS In this prospective evaluation, 25 patients with OSSN with different clock hours of involvement (range, one to eight), age varying from 19 to 76 years, were treated with topical MMC 0.04% in a cyclic manner. Preoperative corneal thickness measurement and endothelial cell density were obtained, and the tests were repeated after one, three, and six months of complete resolution. The fellow eyes of the same patients served as controls. RESULTS Mean +/- standard deviation (SD) pachymetry and endothelial cell counts before and after instillation were 504.48 +/- 5.45 microm and 2325.76 +/- 192.52 cells/mm2 and 503.52 +/- 5.75 microm and 2297.60 +/- 192.08 cells/mm2, respectively, suggesting no significant difference in the above two parameters. Similarly, in the fellow control eyes, mean +/- SD pachymetry and endothelial cell counts before and after instillation were 502.80 +/- 4.34 microm and 2326.72 +/- 191.93 cells/mm2 and 504.64 +/- 5.19 microm and 2313.60 +/- 192.03 cells/mm2, respectively. CONCLUSIONS Topical 0.04% MMC drops do not significantly affect the corneal endothelium. However, its judicious use and long-term follow-up are mandatory.