Combinations of multiple biomarkers representing distinct aspects of metastasis may have better prognosticvalue for breast cancer patients, especially those in late stages. In this study, we evaluated the protein levels ofN-α-acetyltransferase 10 protein (Naa10p), synuclein-γ (SNCG), and phosphatase of regenerating liver-3 (PRL-3) in 365 patients with breast cancer by immunohistochemistry. Distinct prognostic subgroups of breast cancerwere identified by combination of the three biomarkers. The Naa10p+SNCG-PRL-3- subgroup showed bestprognosis with a median distant metastasis-free survival (DMFS) of 140 months, while the Naa10p-SNCG+PRL-3+subgroup had the worst prognosis with a median DMFS of 60.5 months. Multivariate analysis indicated Naa10p,SNCG, PRL-3, and the TNM classification were all independent prognostic factors for both DMFS and overallsurvival (OS). The three biomarker combination of Naa10p, SNCG and PRL-3 performed better in patients withlymph node metastasis, especially those with more advanced tumors than other subgroups. In conclusion, thecombined expression profile of Naa10p, SNCG and PRL-3, alone or in combination with the TNM classificationsystem, may provide a precise estimate of prognosis of breast cancer patients.