This study aimed to investigate the SRY-related higll-mobility-group box 10 (Sox10) expression in the pathological diagnosis of triple-negative breast cancer (TNBC). Furthermore, its correlation with the clinicopathological characteristics and disease-free survival rate in patients with TNBC was also evaluated to identify the diagnostic utility of Sox10 as a reliable biomarker for the diagnosis and prognosis of TNBC.Methods: Using immunohistochemistry (IHC), we identified the expression of Sox10, GATA binding protein 3 (GATA-3), forkhead box protein A1 (FOXA1), gross cystic disease fluid protein (GCDFP15), and mammaglobin (MGB) in 376 cases of primary invasive breast cancer, and 77 cases of metastatic breast cancer.The expression of Sox10 in different molecular subtypes of primary invasive breast cancer and metastatic breast cancer were also compared. Furthermore, the correlation between Sox10 expression and clinicopathological parameters and disease-free survival (DFS) of patients with primary TNBC were also analyzed.Results: Expression of Sox10 was only detected in the myoepithelial cells of normal breast tissue, but not in any other types of cells, including luminal cells and fibroblasts. The positive rate of Sox10 in primary and metastatic TNBC was significantly higher than that in luminal types and human epidermal growth factor receptor 2 (HER2) overexpressed type. The sensitivity and specificity of Sox10 expression in primary TNBC and metastatic TNBC were significantly lower than GATA-3, significantly higher than FOXA1, GCDFP15, and MGB (P<0.001, P=0.0004, P=0.0064, P=0.0229, respectively). In 71 cases of primary TNBC, a higher expression rate of Sox10 was significantly associated with high-grade tumors, late-stage tumors, and tumors with involvement of four or more lymph node metastases (P=0.0145, P=0.0105, P=0.0249, respectively).Conclusions: Sox10 may be used as a novel reliable putative marker for the diagnosis of TNBC. Notably, Sox10 combined with GATA-3 expression may serve as a supplementary differential diagnostic biomarker for primary and metastatic TNBC. Besides, Sox10 may be a good predictor of the prognosis of primary and metastatic TNBC. This study also highlights the significance of targeting Sox10 as a promising potential therapeutic target gene for TNBC therapy.