Soluble CTLA4 (sCTLA4) was assessed in sera of 43 new cases with breast cancer and 44 age- and sex-matched healthy individuals by enzyme-linked immunosorbent assay method. Associations of sCTLA4 levels with the six important CTLA4 Single Nucleotide Polymorphisms (SNPs) and with the resulted haplotypes were investigated. Results revealed significant concentration of sCTLA4 in patients with breast cancer (23.5 ± 14.96 versus 7.69 ± 4.04 ng/ml, p < .001). Patients' sCTLA4 concentration observed to be affected by the SNPs at positions +49 and +1822 and haplotype combination TACACA/TACGTG. These findings suggest that increased sCTLA4 may contribute in CTLA4-induced suppression of tumor immunity and provide explanations for the widely reported association of CTLA4 gene with cancer.