Nurses take care of patients around the clock, so they are in an ideal position to observe and record the signs and symptoms of oral mucositis. This requires a valid, reliable scoring instrument that is easy to use. The objectives of this study were to summarize the scoring instruments that are available, to develop a new Nijmegen Nursing Mucositis Scoring System (NNMSS) and to evaluate this new instrument. A systematic review was undertaken in which 21 scoring instruments were reviewed and compared. None of the instruments studied satisfied the criteria that were established beforehand. The six most common items from the systematic review were selected for the new instrument. To test the NNMSS, pairs of experienced nurses assessed the oral cavity of 26 patients independently. Inter-observer reliability (Kappa), correlation between items (Spearman’s rank–order correlations) and internal consistency of the instrument (Cronbach’s alpha) were calculated. The usability was evaluated with a questionnaire. Cohen’s weighted Kappa was within an acceptable range. Almost all correlations were statistically significant and in the predicted direction. The Cronbach’s alpha coefficient indicated sufficient internal consistency. All nurses found the NNMSS user-friendly and suitable for day-to-day care. The NNMSS can be used as a valid, reliable and usable instrument in daily nursing practice.