Purpose The aim was to prospectively map symptom clusters in patients with stage I–IIIa breast cancer during standard chemotherapy treatment in a randomised study. Methods Participants completed the Memorial Symptom Assessment Scale (MSAS) at baseline, day 12 after the first and third cycle of FEC 75 or FEC 100, and day 12 after the last cycle of Taxotere. Cut-off values for symptom scores, a mean value based on each individual reporting a symptom including occurrence, frequency, severity and distress for inclusion in analysis, were determined. Results The symptom burden cluster analysis was conducted in two steps and included symptoms with high frequency and high levels of distress. The factor analysis revealed three symptom clusters; physical, gastro (phys/gastro) and emotional, with core symptoms that remained stable over time. The most prevalent symptoms for the total sample during all cycles were as follows: lack of energy (range between 48 and 90%), feeling sad (48–79%), difficulty sleeping (54–78%), difficulty concentrating (53–74%), worrying (54–74%) and pain (29–67%). Conclusion In summary, we have prospectively established that symptom clusters remain stable over time with a basis of core symptoms. This knowledge will aid in the development of effective core symptom-focused interventions to minimise symptom burden for patients treated with chemotherapy for breast cancer.