Syk is a non-receptor type of protein-tyrosine kinase that is widely expressed in hematopoietic cells. Syk expression has been reported in breast tissue. However, the function of Syk in breast tissue remains unclear. In 25 (28%) of the 90 paired samples of human breast cancer and the matched, adjacent non-cancerous tissues examined here, reduced mRNA expression of Syk in the breast cancer tissues was observed by real-time quantitative reverse transcription-polymerase chain reaction. Eight (32%) of the 25 cases showing reduced Syk mRNA expression demonstrated distant metastasis of breast cancer, while only 4 (6%) of the 65 cases who did not show reduced Syk expression had distant metastasis. Kaplan-Meier curves demonstrated that patients with reduced Syk expression were at significantly increased risk for distant metastasis (P=0.0003). Our data suggest that reduced Syk expression in breast cancers is associated with distant metastasis and poor prognosis; therefore, Syk is considered to be a potential tumor suppressor and anti-metastasis gene in human breast cancer.