We developed a fast dissolving oral film containing 4 mg dexamethasone and examined the clinical effect of the film as the antiemetic by a randomized controlled crossover study in breast cancer patients receiving a combination chemotherapy with anthracycline and cyclophosphamide, a highly emetogenic chemotherapy. The film was prepared as reported previously using microcrystalline cellulose, polyethylene glycol, hypromellose, polysorbate 80 and 5% low substituted hydroxypropylcellulose as base materials. The uniformity of the film was shown by the relative standard deviation of 2.7% and acceptance value of 5.9% by the Japanese Pharmacopoeia. Patients were administered with 8 mg dexamethasone as oral film or tablet on days 2–4 after chemotherapy in addition to the standard antiemetic medication. The rates of complete protection from vomiting during acute and delayed phases were not different between film-treated group and tablet-treated group. The time course of the complete protection from nausea or vomiting during 0–120 h was also similar between the two groups. Patient's impressions on the oral acceptability in respect of the taste and ease in taking were significantly better for film than for tablet. Therefore, the present fast dissolving oral film containing dexamethasone seems to be potentially useful as an antiemetic agent in patients receiving highly emetogenic chemotherapy.