Sox10 labeling by immunohistochemistry has been primarily reported in tumors of neural crest origin, such as nerve sheath tumors and melanoma. However, Sox10 also labels primary breast carcinomas, particularly those with the basal-like, triple-negative phenotype. However, the utility of Sox10 labeling in metastatic breast carcinomas has not been reported. Here, we prospectively evaluated Sox10 labeling in surgically resected metastatic breast carcinomas from 26 patients sampled on tissue microarrays. In this cohort, Sox10 labeling was seen in 3 metastatic breast carcinomas (12%), all of which were grade III, triple-negative ductal carcinomas metastatic to the brain (n=2) or lung (n=1). Overall, 38% of triple-negative metastases were Sox10 positive, compared to 0% of estrogen receptor (ER) or human epidermal growth factor 2 (HER-2) metastases (P=.045). In addition, we retrospectively reviewed the use of Sox10 immunohistochemistry in metastatic carcinomas in our clinical practice. We identified 21 cases from January 2012-July 2017 in which Sox10 immunohistochemistry was ordered on clinical sign-out in the work-up of a metastatic carcinoma as being of possible breast origin. Overall, Sox10 labeled 57% (n=12) of all evaluated metastatic carcinomas. All of the Sox10 tumors were ER, such that 71% of ER carcinomas were Sox10 in comparison to 0% of ER carcinomas (P=0.049). In conclusion, the differential diagnosis of a Sox10 malignancy of unknown origin should not be limited to metastatic melanoma. Sox10 labeling is seen in a subset of metastatic triple-negative breast carcinomas, supporting its use as a marker of breast origin in this setting.