Desmopressin (DDAVP) is a synthetic vasopressin analog with hemostatic properties that can be used to prevent bleeding in surgery. Previously, we demonstrated that perioperative administration of DDAVP dramatically reduced lymph node involvement and lung metastasis in a mouse model of mammary tumor manipulation and surgical excision. In this study, the effect of DDAVP was evaluated in the surgical treatment of bitches suffering from spontaneous mammary gland tumors. Intact bitches with locoregionally advanced mammary gland cancer (stages III and IV) confirmed by deferred biopsy were included. Tumors and regional lymph nodes were excised. Treated animals (n=13) were administered intravenously with two doses of DDAVP (1 μg/kg/dose), 30 min before and 24 h after surgery. Control animals (n=13) received the saline vehicle. Tumors were diagnosed as carcinoma (n=11), osteosarcoma (n=1), or carcinosarcoma (n=1) in the control group, and carcinoma (n=11) or osteosarcoma (n=2) in the DDAVP group. Six of 13 (46%) control bitches had locoregional recurrence or metastasis within the 3 months after surgery, while only 1 of 13 (7%) DDAVP-treated animals did (p=0.03; chi2). The disease-free survival median time was significantly higher in DDAVP-treated animals (Control: 105 days versus DDAVP: >318 days; p<0.05 log-rank test). These preliminary results support the potential utility of the neoadjuvant perioperative treatment with DDAVP in advanced mammary tumors.