Background: In a randomized controlled trial, compared with standard care alone in breast cancer, acupuncture as a prophylactic treatment did not show better quality of life or fewer side effects of chemotherapy (NCT01727362 [clinicaltrials.gov]). The aim of the qualitative part of this mixed methods study was to better understand the subjective perspectives of the patients regarding quality of life during chemotherapy and the perceived effects of acupuncture. Methods: In a nested retrospective qualitative study, semi-structured telephone interviews were conducted with 5 responders and 5 non-responders (defined by the outcome of the primary parameter FACT-B) who were randomly selected from both study arms. The interviews were digitally recorded, pseudonymized, transcribed, and then deductively and inductively analyzed according to Qualitative Content Analysis using MAXQDA® software. Results: A total of 20 patients were included in the qualitative part of the study. In both groups, most women stated that their quality of life was surprisingly better than what they had expected before starting the chemotherapy. All patients of the acupuncture group experienced the acupuncture treatments as relaxing and beneficial, mentioning a friendly setting, and empathic attitude of the therapist. Most of these patients stated that the acupuncture treatment reduced chemotherapy-induced side effects. The patients reported that acupuncture was supportive for coping with the disease in a salutogenic way. For all patients, finding strategies to cope with life-threatening cancer and the side effects of chemotherapy was essential, for example, keeping a positive attitude toward life, selecting social contacts, and staying active as much as possible. Conclusions: Patients in the acupuncture group reported positive effects on psychological and physical well-being after receiving the study intervention. For all patients, having coping strategies for cancer seemed to be more important than reducing side effects. Therefore, further studies should focus more on coping strategies and reducing acute side effects.