Triple negative breast cancer (TNBC)-defined by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 negativity is a group with poor prognosis, due to aggressive tumor biology and lack of targeted therapy. Topoisomerase II-α (topoIIα) protein is one of the intracellular targets for anthracycline-based therapy, and high levels of topoIIα expression are recently observed in TNBC. The study included 83 patients who underwent surgery between January 2003 and December 2009. Paraffin blocks were stained immunohistochemically with CK5/6, CK14, EGFR, Ki-67, and topoIIα. Basal-like (BL) immunophenotype was defined by positivity for ≥1 basal cell markers: CK5/6, CK14, or EGFR. Of 83 TNBC, 66.26% were of the BL immunophenotype, which was significantly associated with higher mitotic count (P=0.023), BL morphology (P=0.005), higher histologic grade (P=0.022), and higher proliferation rate assessed by Ki-67 (P<0.001). TopoIIα expression was significantly correlated with invasive ductal carcinoma NOS (P=0.010), higher mitotic count (P=0.001), higher histologic grade (P=0.007), and higher Ki-67 (P<0.001). In conclusion, due to lack of expression of ER, PR, and human epidermal growth factor receptor 2 receptor in TNBC, specific targeted therapies are not effective, and chemotherapy is currently the only modality of available systemic therapy. Due to expression of topoIIα, anthracyclines may be effective in treatment of TNBC.