Abstract Background: Retinoblastoma (RB) is a rare inherited eye disease. Leukocoria is the first presenting sign of this disease. Early diagnosis is important to gain better life outcomes. Aim of Study: A cross-sectional study was performed using a web-based questionnaire to collect data. We analyzed the data using the SPSS program. Material and Methods: We aim to assess Kafr El-Sheikh University Medical Students' knowledge about retinoblastoma. Results: We survived 235 medical students and graduates at Kafr El-Sheikh University. Most participants (n=131, 55.7%) had sufficient knowledge about retinoblastoma, while 78 (33.2%) had poor knowledge. Only 26 (11.1 %) had a proficient level. Almost all participants (99.6%) detected that the abnor-mal eye was due to disease. Nearly two-thirds (63%) thought that it was a life-threatening leukocoria. While (96.6%) knew that, an ophthalmologist referral was the right thing to do. We found no significant differences between academic grades and test results (H=1.093, p=.779). As well, no correlation was found between academic grades and results (r=.033, p=.086). Conclusion: Retinoblastoma is a fatal disease that needs attention in developing countries. Early detection of RB is the key to successful management with a higher survival rate. All healthcare providers, particularly those who have direct contact with children, should receive comprehensive education to improve their clinical screening skills.