Summary:Three hundred and forty‐five dogs with mammary tumors were initially evaluated for study. One hundred and forty‐four dogs with untreated malignant mammary tumors (136 adenocarcinomas, 5 malignant mixed, 3 sarcomas) were selected for study. All dogs were clinically staged and stratified on the basis of tumor volume and body weight. Dogs were randomized to either a radical mastectomy or simple mastectomy group, and then further randomized to a levamisole or placebo group. There was no significant difference in either survival time or cancer‐free survival time between the surgery groups or between the levamisole and placebo groups. The most significant prognostic factor was tumor volume; dogs with tumors <41 cc had significantly enhanced survival time (p = 0.0007) and cancer‐free survival time (p = 0.0005).