Recently, we showed the implication of the polymorphism in tumor necrosis factor-alpha (TNF-alpha) gene in the susceptibility and prognosis of breast carcinoma. TNF-alpha acts through its receptors: types I and II. The TNFRII, expressed on the haematopoietic cells, is the high affinity receptor involved in mediating the biological effects of TNF-alpha. We investigated the susceptibility and prognostic implications of the genetic variation in the TNFRII in breast carcinoma. We used the polymerase chain reaction and restriction enzyme digestion to characterize the variation of the TNFRII gene in 300 unrelated Tunisian patients with breast carcinoma and 200 healthy control subjects. Associations of the genetic marker with the rates of the breast carcinoma-specific overall survival and the disease-free survival were assessed. A significant association was found between TNFRII-196M/R heterozygous genotype and breast carcinoma (OR = 1.61; P = 0.02). This association was more significant in post-menopausal patients (OR = 2.41, P = 0.0001). The 196R-TNFRII allele showed a significant association with increased overall survival and disease-free survival in breast carcinoma patients. Genetic variation in TNFRII may predict the late onset of breast carcinoma, relapse and death for patients with breast carcinoma.