BACKGROUND Oral mucositis (OM) is an inflammation of the oral mucosa which occurs in 20-40% of patients receiving conventional chemotherapy (CM). Many different substances have been used separately to treat or prevent OM but no standard procedure has been settled as definitive. We conducted a prospective study to examine whether rinses with a mixture of soluble prednisolone, nystatin and salt water applied before the expected OM appears, would reduce the incidence of grade 2-3 OM in subsequent cycles of CM. METHODS Prospective study of breast cancer patients undergoing neoadjuvant or adjuvant treatment with FEC (5 fluorouracil, epirubicin, cyclophosphamide) or docetaxel who developed OM grade 2 or 2-3 with the previous cycle. The specific mouthwash consisted of a combination of 100 mL of water, 5 mg of soluble prednisolone, 2 drops of nystatin and 2.300 mg of salt (1 teaspoon). Patients received clear instructions on how to use it. The primary end-point was the incidence of OM grade 2-3 with the following cycle of CM. Secondary end-points were the rate of CM dose reduction (DR) and the incidence of OM grade 0, 1 and 2 with the following treatment. RESULTS Sixty-eight patients were included. Twenty-three developed OM grade 2-3 after first cycle. After using this mouthwash, only two cases developed grade 2-3 OM. Only four cases needed a CM DR. CONCLUSIONS Our study showed a significant reduction in the rate of OM grade 2-3 in patients using the especial mouthwash. This mouthwash is currently used as standard in our institution. Further evaluation in other centres to confirm these results is needed.