Previous studies showed that various immune stimulants in CaD2 mammary adenocarcinomas were effective in controlling tumour growth. The objective of this study was to evaluate the efficacy of cyclosphophamide (CY) in combination with levamisole (LE) as an adjuvant therapy to surgical resection of canine mammary tumours. Thirty bitches of various breeds presenting malignant mammary tumours were attended at a public veterinary hospital (São Paulo, Brazil) and randomly divided into 2 groups - those submitted to surgical procedure alone (group I, n=15) and those in which was used the association of surgery and a combination of CY and LE (group II, n=15). Mammary tumours were assigned based on the WHO Tumour-Node-Metastasis (TNM) classification. Depending on the specific case, the surgical procedure consisted of regional or complete unilateral mastectomy. Chemotherapy was done using CY (50mg/m2, twice a week, v.o.) and LE (2,5mg/kg, three times a week, v.o.) during 2 months. For a period of 2 years each bitch was regularly monitored by laboratory tests and clinically for local recidives and metastases. In all cases, mammary tumours were detected by the owner one month to one year before the first clinical examination. The mean age of the dogs at diagnosis was 9 (± 1,5) years and there was no statistical association between these tumours and history of pseudopregnancy, parity, estrus irregularity and anticonceptional therapy. Group I presented 4 bitches with tumours assigned as TNM stage I, 8 with TNM stage II and 3 with stage III. Histopathological classification of these tumours resulted in 9 cases of tubulopapillary carcinomas and 6 cases of solid carcinomas. Lymph node or lung metastases were not found in none of these patients before surgery, but one year after surgical resection, 7 animals (46,7%) presented local recurrences and metastases, and euthanasia was demanded by the owner. In group II, 3 bitches had tumours with TNM stage I, 9 with stage II and 3 with stage III. Histopathological analysis showed 10 tubulopapillary carcinomas and 5 solid carcinomas. One female dog presented severe leucopeny, demanding the interruption of treatment. Only 2 animals (14,3%) presented local recurrences and metastases. Thus the present study showed that a combination of surgery and use of CY/LE revealed to be a better method of therapy for malignant canine mammary neoplasms than tumour resection alone.