Abstract Introduction Prolactin-secreting adenoma (PRLoma) can present as large and invasive neoplasm, with increased markers of cellular proliferation. First-line approach is Dopamine Agonists (DAs) treatment; however, DA-resistance has been reported, especially in male patients. Estrogens induce lactotroph cell replication and PRL secretion: the use of anti-estrogen treatment in patients with PRLoma have been described in few cases. We reported our experience regarding treatment with the aromatase inhibitor anastrozole (ANA) as add-on therapy for male patients with DA resistant PRLoma. Materials and methods We describe four male patients (26, 38, 29 and 19 years old at diagnosis), with PRLoma (median diameter 26 mm, PRL 7730 μg/L). They were resistant to cabergoline (CAB, > 2 mg/week) in terms of PRL secretion and tumor size reduction. ANA 1 mg/day was added to the maximum tolerated dose of CAB for at least 1 year. Magnetic Resonance was performed at baseline, after 6 months of CAB + ANA combination and every 12 months afterward. Results PRL levels decreased in all patients after CAB + ANA (mean − 70%, range − 44/− 97%), achieving a normalization of PRL levels in one case. Tumor size decreased in all cases (mean − 47%, range − 24.5/− 68%). No severe adverse effects have been reported, a moderate weight gain has been observed in two cases. Conclusions Addition of an aromatase inhibitor (ANA) to the dopamine agonist therapy improved the control of prolactin levels and induced tumour regression.