We present a case report of a patient with a rare high-grade transformation of an acinic cell carcinoma (ACC) of the parotid gland, who developed Cushing’s syndrome (CS) as a result of ectopic secretion of adrenocorticotropic hormone by the tumour. The hypercortisolism was successfully treated with metyrapone, and the ACC was treated with local radiotherapy and a combined six cycles of gemcitabine and cisplatin, having achieved a partial response to the tumour. A multidisciplinary approach and combined medical treatment with radiotherapy and were essential for disease control and CS management. ACC should be considered in the differential diagnosis of ectopic CS.