Breast cancer causes numerous physical complications and mental stress that negatively impact patients' performance and quality of life. This study examined the effects of mindfulness-integrated cognitive behavior therapy (MICBT) on depression, anxiety, stress, and sleep quality in women with breast cancer. A clinical trial design with pre-tests and post-tests and a two-month follow-up were used in the current study. The target population was women with breast cancer, 30 of whom were selected through purposeful sampling. Then, 15 participants were placed in the intervention group and 15 in the control group with four random blocks. Those in the intervention group received mindfulness-integrated cognitive behavior therapy, while those in the control group received self-help (an educational book). Demographic questionnaires, the Depression, Anxiety, Stress Scale (DASS-21), and Pittsburgh Sleep Quality Index (PSQI) were used to collect data. Descriptive statistics such as frequency, mean and standard deviation, repeated measures ANOVA, and the Bonferroni test were used to analyze the data. The maximum alpha error level was considered 0.05 to test the hypotheses (p ≥ 0.05). The results showed the effectiveness of MICBT therapy on depression, anxiety, stress, and sleep quality (p < 0.05). The mean scores decreased in all variables, including from 15.47 ± 1.77 in the pre-test to 11.33 ± 4.25 in the post-test for depression, from 13.20 ± 2.60 in the pre-test to 8.67 ± 4.19 in the post-test for anxiety, from 19.73 ± 1.98 in the pre-test to 14.67 ± 2.69 in the post-test for stress and from 9.20 ± 1.74 in the pre-test to 5.07 ± 2.05 in the post-test for sleep quality. Based on the results of this study, it can be concluded that MICBT therapy is effective in reducing depression, anxiety, and stress and improving sleep quality in women with breast cancer. Therefore, it is recommended that affected women use psychological treatments such as MICBT in addition to medical treatments to deal with this stressful and challenging disease. MICBT can improve mood, offer a new cognitive and behavioral system, change patients' habits and thought patterns, and improve their lifestyle.