Dopamine receptors was suggested to be expressed in medullary thyroid cancer (MTC). The aim of the current study was to evaluate the expression of D2 dopamine receptor in MTC and the effectiveness of the dopamine agonist cabergoline in patients with MTC. Five paraffin-embedded cases of MTC obtained after thyroidectomy were used to evaluate D2 receptor expression by immunohistochemistry. Fifteen patients (7 males, 8 females, 3678 years) with post-surgical persistent and not operable MTC were treated with cabergoline for 4 months, in order to evaluate its effect on clinical syndrome, serum calcitonin (CT) and CEA levels, and metastasis number and size. Cabergoline was administered at the dose of 1 mg/week for the first month and 3.5 mg/week for the following 3 months. D2 receptor was variably expressed in all 5 cases of MTC. Before treatment, all patients had progressively increasing serum CT and/or CEA levels. Lymph node metastasis were visible in 4, whereas liver and lung metastasis were identified in 1 and 2 patients, respectively. At the 4-month follow-up, a significant decrease of serum CT (P=0.027) but not CEA (P=0.244) levels was found. A >50% decrease in serum CT levels was found in 3 (20%), a 2550% decrease was found in 10 (66.7%) and an increase in serum CT levels was found in 2 (13.3%) patients. A significant improvement in flushing (P=0.039) and fatigue (P=0.023) and a slight improvement in diarrhoea (P=0.066) score was also found. No significant change was found in body weight. No significant change was observed in metastasis number and size, although one patient experienced a disease progression. In conclusion, the results of this study demonstrated that D2 receptor is expressed in MTC and that cabergoline treatment improve clinical syndrome and decrease serum CT levels in patients with post-surgical persistent MTC. Further studies on a larger number of patients and longer period of treatment are mandatory to draw definitive conclusions on the usefulness of cabergoline treatment in patients with MTC.