BackgroundApproximately 10%–15% of patients with breast cancer die of cancer metastasis or recurrence, and early diagnosis of it can improve prognosis. Breast cancer outcomes may be prognosticated on the basis of surface markers of tumor cells and serum tests. However, evaluation of a combination of clinicopathological features may offer a more comprehensive overview for breast cancer prognosis. Materials and methods We evaluated serum human epidermal growth factor receptor 2 (sHER2) as part of a combination of clinicopathological features used to predict breast cancer metastasis using machine learning algorithms, namely random forest, support vector machine, logistic regression, and Bayesian classification algorithms. The sample cohort comprised 302 patients who were diagnosed with and treated for breast cancer and received at least one sHER2 test at Chang Gung Memorial Hospital at Linkou between 2003 and 2016. Results The random-forest-based model was determined to be the optimal model to predict breast cancer metastasis at least 3 months in advance; the corresponding the area under the receiver operating characteristic curve value was 0. 75 (p < 0. 001). Conclusion The random-forest-based model presented in this study may be helpful as part of a follow-up intervention decision support system and may lead to early detection of recurrence, early treatment, and more favorable outcomes.