Background Chromosome region maintenance-1 (CRM1) is a protein that is essential for maintaining chromosome structure. Zinc fingers and homeoboxes (ZHX) family members are transcription factors containing two motifs of zinc-finger and five domains of DNA-binding homeobox and are located in the nucleus of cells. ZHXs mainly ZHX3 might have a role in the progression of many cancers. Aim The authors aimed to assess the protein expression of CRM1 and ZHX in triplenegative breast cancer (BC) molecular subtype to detect their roles in BC progression aiming at improving prognostic stratification and therapeutic targets for such aggressive subtype. Patients and methods The authors have measured the expression of CRM1 and ZHX3 in 60 tissue samples retrieved from patients with BC and 20 samples taken from adjacent nonneoplastic breast tissue using immunohistochemistry. We followed patients for five years and analyzed the correlations between CRM1 and ZHX3 levels of expression and clinicopathological parameters, disease recurrence, survival rates, and prognosis of patients. Results CRM1 high expression and ZHX3 low expression were detected in BC more than non-neoplastic breast tissues (P=0.009 and 0.028, respectively). High CRM1 expression and low ZHX3 expression were associated with higher grade of the tumor (P=0.013), presence of lymphovascular invasion, lymph node, distant metastases, and unfavorable recurrence-free survival and overall survival (OS) rates of patients with BC (P<0.001). Conclusion The authors found that increased CRM1 expression and decreased ZHX3 were related to tumor progression and dismal outcome in patients with triple-negative breast cancer.