We aimed to determine changes in the expression of the genes CDH1, CDH13, CD44, and TIMP3 to look for any relationship between them, HER2 and ESR1 expression at the RNA level, and the histopathological properties of tumors. We also analyzed the expression properties of double-negative (estrogen receptor [ER] and human epidermal growth factor receptor [HER2] both negative) breast tumors. Expression status was studied in fresh tissue at the mRNA level with quantitative PCR using hydrolysis probes. Sixty-two cancer patients and four normal controls were included in the study. When the tumor group was analyzed as a whole, the correlations of ESR1 with CDH1, CDH13, and TIMP3 were P < 0.05, P < 0.005, and P < 0.005, respectively. In ER-positive tumors, CDH1 and CDH13 were correlated directly (P < 0.005) when HER2 was correlated with CDH1, CDH13, and TIMP3 indirectly (P < 0.005, P < 0.005, and P < 0.05, respectively). CDH1 and CD44 had a strong indirect correlation (P < 0.005) in ER-negative tumors. There were significant differences in the expression levels of the CDH13, TIMP3, and CD44 genes (P < 0.005, P < 0.005, and P < 0.05, respectively) between the ER-positive and -negative groups. All four genes were found to be correlated with invasive properties in both ER-positive and -negative tumors. In double-negative tumor samples, only CD44 had a significant and strong correlation with stage, lymph node involvement, and metastasis (P < 0.05, P < 0.005, and P < 0.05, respectively). As a conclusion, a decrease in CDH1, CDH13, and TIMP3 expression levels with an increase in CD44 can be used as an indicator for invasion in both ER-positive and -negative breast tumors. In double-negative tumor tissues, CD44 can be considered a marker for aggressive properties. (Cancer Sci 2009; 100: 2341-2345 B reast cancer is the most common type of cancer and the most important cause of mortality and morbidity related to cancer in industrial countries. Several molecular markers for predicting response to treatment and prognosis have been introduced. The status of estrogen receptor (ER), which is a member of the ER nuclear receptor superfamily, is one of the most declared markers. Transcription of ER and estrogen is regulated by complicated mechanisms. Two isoforms of the ER (ER-a and ER-ß), which mediates the steroid hormone estrogen, are present; both have similar estrogen binding affinities but their expression is regulated separately.(1)The role of ER-ß expression in breast cancer is not yet clear, but the presence of ER-a (ESR1) is used as a marker to indicate the potential effectiveness of endocrine treatment.(1)Almost one-third of breast tumors are ER negative at the time of diagnosis, and some others loose their receptors during tumor progression.(2) Mostly ER-positive tumors have a better prognosis then ER-negative tumors. They can be successfully treated with hormone therapy like tamoxifen and aromatase inhibitors. (3,4) Epidemiological studies have shown that ER-positive tumors have a different risk profile compared with ER-neg...