Background <p>Cancer ranks as the second leading cause of mortality on a global scale. Individuals afflicted with cancer commonly experience detrimental psychological symptoms, including fear, anxiety, and depression. Physical activity represents a viable strategy for mitigating the symptoms of cancer. This study investigated the impact of physical activity on health perception and mental health in Iranian women with breast cancer.</p> Methods <p>A cross-sectional study was conducted on a sample of 158 women diagnosed with breast cancer admitted to the outpatient oncology unit of a public hospital in Iran between June and October of 2023. We used two questionnaires for data collection and chi-square, logistic regression models, and MANOVA for data analysis facilitated by SPSS.</p> Results <p>Study findings indicated a statistically significant difference in mental health status among patients who engaged in different levels of physical activity (<i>F</i> = 7.289, <i>η</i>² = 0.001, <i>p</i> &lt; 0.05). The results of a multivariate-adjusted model also highlighted the predictive role of high level of physical activity (OR = 0.55; CI 95% = 0.13–0.78) and moderate level of physical activity (OR = 0.72; CI 95% = 0.55–0.96) on mental health status of cancer patients.</p> Conclusion <p>Our findings demonstrate that engaging in moderate to high levels of physical activity is associated with better mental health outcomes and improved health perceptions among breast cancer patients. We found that patients who engaged in moderate physical activity reported better mental health conditions than those who were inactive. Furthermore, our study revealed that socio-demographic factors such as education level, employment status, and marital status play a significant role in the mental health status of breast cancer patients. Our findings support the integration of physical activity promotion into breast cancer care protocols.</p>