Recently, a significant number of breast cancer (BC) patients have been diagnosed at an early stage. It is therefore critical to accurately predict the risk of recurrence and distant metastasis for better management of BC in this setting. Clinicopathologic patterns, particularly lymph node status, tumor size, and hormonal receptor status are routinely used to identify women at increased risk of recurrence. However, these factors have limitations regarding their predictive ability for late metastasis risk in patients with early BC. Emerging molecular signatures using gene expression-based approaches have improved the prognostic and predictive accuracy for this indication. However, the use of their based-scores for risk assessment has provided contradictory findings. Therefore, developing and using newly emerged alternative predictive and prognostic biomarkers for identifying patients at high- and low-risk is of great importance. The present review discusses some serum biomarkers and multigene profiling scores for predicting late recurrence and distant metastasis in early-stage BC based on recently published studies and clinical trials.