Triple negative breast cancers (TNBC) are clinically heterogeneous but mostly aggressive malignancies devoid of expression of the estrogen, progesterone and HER2 (ERBB2 or NEU) receptors. Recent evidence shows that basal endoplasmic reticulum stress (ERS) is typically activated in TNBC and cooperates with hypoxia signaling to promote tumor progression and relapse; ERS and hypoxia response may therefore be among the long-searched hallmarks of TNBC.