The aim of the study was to evaluate the incidence of adverse events (AEs) in female dogs diagnosed with advanced clinical stage mammary gland neoplasms following treatment with thalidomide. A prospective analysis of 29 female dogs treated with a high dose (HD) of 20 mg/kg/day of thalidomide for three months followed by a low dose (LD) of 10 mg/kg/day of thalidomide for three months was performed. All patients underwent physical examination, complete blood count, serum biochemistry profile, thoracic radiographs, and abdominal ultrasound analysis before the treatment and after the HD and LD. Clinical AEs were absent in 16/29 (55.17 per cent) patients following HD. An initial 3-5 day period of somnolence was described in 4/29 (13.79 per cent), prolonged somnolence in 5/29 (17.24 per cent), a short period of somnolence lasting only a few hours in 3/29 (10.34 per cent), and difficulty to rouse was described in 5/29 (17.24 per cent) cases. Two patients (6.89 per cent) presented with prolonged somnolence that interfered with activities of daily living, resulting in anticipation of the dose reduction to the proposed LD after 15 days of the HD treatment. Following dose reduction, AE improvement was observed in all patients. Albeit remaining within the reference ranges, erythrocytes, haematocrit, total leucocyte count, neutrophils, lymphocytes, monocytes and γ-glutamyltranspeptidase showed significant alteration associated to thalidomide treatment.