OBJECTIVE To evaluate natural killer (NK) cells activity in breast cancer patients and its comparison with normal individuals. METHODS Breast cancer is the most prevalent type of spontaneous tumor in humans, and NK cells are the first line defense against such tumors. There is a reverse correlation between NK activity and metastasis and reducing the tumor mass by surgery may be monitoring the NK activity. In this study, we evaluate NK activity in pre and post mastectomy patients. METHODS Eighteen patients with invasive ductal carcinoma attended to cancer research institute were included in this study. NK cells were evaluated in pre and post mastectomy patients. PBMCs were isolated by ficoll hypaque. NK cell activity (% lysis of K562) was evaluated by flow cytometer. METHODS One way analysis of variation (ANOVA) and Kruskal Wallis nonparametric test were employed using SPSS software. RESULTS While NK cell activity was greatly impaired in breast cancer patients (average lysis of K562 target cells: 24.4% vs. 62.5% in healthy controls, n = 18), it was found to be significantly increased after mastectomy (37.7%). CONCLUSIONS Mastectomy may lead to increased activity of NK cells among patients suffering from breast cancer and their increased activity may produce positive therapeutic effect.