The receptor for CCL22 is named CCR4 that preferentially is expressed on the regulatory T cells (Treg), and accordingly, CCL22 acts as a chemoattractant for the intratumoral Treg migration. The aim of this study was to evaluate the serum CCL22 levels and a single nucleotide polymorphism (SNP) in chemokine gene, [2030 G/C (rs223818)], in patients with breast cancer. Blood samples were collected from 100 women with breast cancer before receiving chemotherapy, radiotherapy, or immunotherapy and 100 age-matched healthy women as a control group. The serum CCL22 levels were measured by ELISA. The DNA extracted and the SNP rs223818 determined by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique. The mean serum CCL22 levels in patients with breast cancer (2398.5 ± 123 Pg/mL) was significantly higher in comparison to healthy control group (974.2 ± 39.9 Pg/mL; P < 0.001). According to the tumor stages, the mean serum levels of CCL22 were 999.8 ± 85.0 Pg/mL in stage I, 1718.8 ± 82.3 Pg/mL in stage II, 2846.8 ± 118.0 Pg/mL in stage III, and 3954.5 ± 245.2 Pg/mL in stage IV. There was significant difference between tumor stages regarding the serum CCL22 levels (P < 0.001). In patients with breast cancer, the frequencies of CC genotype (63%) and C allele (79%) at rs223818 were significantly higher as compared to healthy controls (31 and 52%, respectively; P < 0.001). In both patients and control groups, the mean serum levels of CCL22 in subjects with CC genotype or C allele at rs223818 were also significantly higher as compared to subjects with GG genotype or G allele (P < 0.001). Higher serum CCL22 levels were observed in patients with breast cancer that is increased with advanced stages. These findings represent that the CCL22 may contribute in tumor development. The CC genotype and C allele at rs223818 were more frequent in breast cancer patients. The serum CCL22 levels were affected by genetic variations at SNP rs223818. Accordingly, SNP rs223818 may play a role in the susceptibility to breast cancer.