Background: TNBC patients have a relatively poor prognosis and the optimal choice of chemotherapy for this subgroup has not yet been defined. Studies have shown TNBC is a heterogeneous group of tumours and certain subgroups of TNBC could benefit from neoadjuvant therapy. In this study, we hypothesized that Bcl2 immunohistochemical expression could accurately stratified TNBC into low- and high risk patients and predict their response to chemotherapy. Methods: Three independent series of BC were immunohistochemically profiled for Bcl2; a) 296 and 153 of primary TNBC and non TNBC respectively, in which adjuvant CMF chemotherapy was given, b) 63 TNBC and 160 non-TNBC locally advanced primary BC treated with anthracycline-based chemotherapy c) 31 TNBC and 209 non-TNBC in which all patients were primarily treated with surgery followed by anthracycline-based chemotherapy. Results: In patients with TNBC who received CMF chemotherapy, multivariate Cox regression models demonstrated that Bcl2 was significantly associated with patient outcome; TNBC/ low Bcl2 tumours were associated with a three-fold increased risk of death ((p=0.000039) and recurrence ( p =0.0001) compared to TNBC/high Bcl2 tumours. In patients with BC treated with neoadjuvant anthracycline based chemotherapy, 18/63 (28%) TNBC achieved a pathological complete response (pCR) vs. 17/144 (12%) of non-TNBC (p=0.006). 42% of TNBC with low level of Bcl2 achieved pCR compared with 11% of TNBC with high Bcl2 expression (p=0.02). After neoadjuvant treatment, patients with TNBC with low and high Bcl2 expression had similar clinical outcome. Conclusions: In patients with TNBC who received CMF chemotherapy, Bcl2 expression reclassified patients into two groups: low risk (Bcl2+) versus high risk (Bcl2-) of BC mortality and recurrence. Anthracycline based neoadjuvant therapy is an effective treatment for TNBC with low levels of Bcl2 expression and is associated with a higher pCR rate. Adding Bcl2 to the panel of TNBC phenotype markers could help guide treatment decisions in this group of patients and ultimately lead to better patient outcome.