The differences in the molecular expression within triple-gnegative breast cancer (TNBC) could explain the variable treatment responses seen in this subtype of tumors. Although there is an overlap between TNBC and basal-like breast cancer, they are not the same and the triple-negative phenotype cannot be used as a surrogate of basal-like breast cancer. Multiple studies have shown a close association between BRCA1 pathway dysregulation and TNBC. The claudin-low subtype of breast tumors has high levels of epithelial-to-mesenchymal transition inducer genes, characterized by a rich immune cell infiltrate, cancer stem cell-like features and resistance to chemotherapy. The identification of amplified genes with consistent overexpression may represent mutational drivers and targets for drug development. There is a frequent activation of the PI3K/AKT and RAF/MEK/MAPK pathways in TNBC. TNBC has an increased chemosensitivity and presents with higher response rates to neoadjuvant chemotherapy including anthracyclines and taxanes. The understanding of the molecular features underlying TNBC will be paramount to tailor clinically meaningful therapies.