Breast cancer patients may encounter a wide range of physical and psychosocial distress symptoms during diagnosis, while awaiting treatment, and during treatment. This study of newly diagnosed breast cancer patients explores: (1) changes in symptom distress over 4 months; and (2) factors predicting changes in symptom distress. Methods: A prospective longitudinal design was used to collect data from breast cancer patients in northern Taiwan. A set of questionnaires was used to measure anxiety, symptom distress, social support, and demographic and treatment-related characteristics. Repeated measures analysis of variance (RM-ANOVA) with least significant difference (LSD) was used to examine differences in symptom distress, state anxiety, and social-support levels across four time-points. Generalized estimating equation (GEE) is used to determine predictors for the change in symptom distress. Results: Participants showed mild overall symptom distress during treatment that increased from cancer diagnosis to treatment phases, with a peak at 4 months after diagnosis. Insomnia was the most commonly identified distressful symptom over time. Changes in overall symptom distress were significantly predicted by state anxiety, health professional support, and time since cancer diagnosis. Conclusion: Change in symptom distress following the first 4 months after diagnosis was predicted by state anxiety, health professional support, and time. Patients should receive social support and be trained in problem-solving skills to relieve distressful symptoms from diagnosis through treatment.