Summary A 19‐year‐old Quarter Horse gelding presented with a 6‐week history of hypersalivation, halitosis and dysmasesis. Oral examination revealed retention of food and saliva and the presence of a raised, nodular, 6 × 7 cm, ulcerated mass on the dorsal surface of the tongue base. The mass was confirmed histologically as squamous cell carcinoma. Complete resection of the mass was not possible and surgical laser debulking was followed 15 days later by chemotherapy with a combination of meloxicam and cyclophosphamide in metronomic regimen. After one week, there was a significant improvement in clinical signs and food consumption returned to normal. Therapy was well tolerated with no alteration in haematological or urinalysis parameters. After 5 months of excellent life quality, the horse showed progressive difficulties in mastication and swallowing. Endoscopic examination showed extension of the tumour to all the aboral aspect of the tongue and, with the owner's consent, the patient was subjected to euthanasia. This is believed to be the first report on the combined use of meloxicam and cyclophosphamide in a metronomic fashion for management of an oral squamous cell carcinoma in a horse. Since metronomic therapy is less expensive than conventional chemotherapy, easily administrable and well tolerated, it should be considered as a possible treatment option for nonresectable equine malignant tumours.