Objectives To evaluate how women react to a decision aid (DA) informing them of the harms and benefits of mammography, including overdiagnosis. Background Breast cancer is the most common cancer affecting women. In efforts to reduce mortality, mammography has been widely accepted as an effective method of early detection. However, there is a balance between the known harms and benefits of breast cancer screening. Overdiagnosis is the detection of a cancer that would never cause harm over the lifetime. Comprehension and acceptance of overdiagnosis can be difficult for some people. Design Qualitative study using a semistructured interview protocol. Data were analysed in Atlas.Ti and the framework method was used to identify themes. Setting Telephone interviews with participants living in the USA. Participants 30 female individuals aged 39–49, selected from a nationally representative US sample of individuals who had completed a survey <2 weeks prior, during which they viewed a DA describing the main harms and benefits of breast cancer screening. Results Six major themes were identified: (1) overdiagnosis and false positives were often conflated, (2) previous experience and the influence of doctors and family supersedes new information, (3) beliefs about cancer dominate acceptance and comprehension of overdiagnosis, (4) emotional reactions to the novelty of overdiagnosis, (5) reactions to screening benefits—“I’ll be the one”, and (6) people reported the DA is credible, but they remained sceptical and performed their own research. Conclusion This study provides insights into the challenges of communicating about the harms of breast cancer screening, particularly overdiagnosis. While it is critical to honestly communicate with patients about the harms of breast cancer screening, it is also important to consider the emotional impact of conveying such information. Data are available in a public, open access repository. Data are available on the Open Science Framework, [dataset] Scherer L, Suresh K, Mosley B, Frempong J. Data from: R37 Ipsos breast cancer screening survey and qualitative interviews. Open Science Framework, March 4, 2022. <https://osf.io/y8stc/>