Objective: To detect the expression of KiSS-1 and S100A4 in the primary tumor tissues and lymphatic and visceral metastases and investigate its role in tumorigenesis and metastasis of gastric cancer. Methods: The protein expression of KiSS-1 and S100A4 in lymphatic and visceral metastases from advanced gastric cancer specimens was mainly examined by immunohistochemical staining and tissues microarray. Results: Immunohistochemical staining revealed reduced expression of KiSS-1 and up-regulated expression of S100A4 in lymph node and visceral metastases. Rates of KiSS-1 expression in normal tissues, primary tumor tissues, lymph node and visceral metastases were 95.8%, 74.6%, 60.9% and 57.5%. S100A4 expression in associated cases was 43.6%, 71.8%, 70.3% and 90.0%, respectively. Significant differences in KiSS-1 expression was signifi- cantly higher in normal tissues than that in primary tumor tissues (P<0.001). While significant differences of S100A4 expression could be seen between normal and cancer tissues (P<0.001) and between visceral and primary tumors (P<0.05). Conclusion: Tumor metastasis results from gradual accumulation of abnormal genetic alterations. Down-regulation of KiSS-1 and up-regula- tion of S100A4 play a critical role in metastasis of gastric carcinoma. Objective: To detect the expression of KiSS-1 and S100A4 in the primary tumor tissues and lymphatic and visceral metastases and investigate its role in tumorigenesis and metastasis of gastric cancer. Methods: The protein expression of KiSS-1 and S100A4 in lymphatic and visceral metastases from advanced gastric cancer specimens was primarily examined by immunohistochemical staining and tissues microarray. Results: Immunohistochemical staining revealed reduced expression of KiSS-1 and up-regulated expression of S100A4 in lymph node and visceral metastases. Primary tumor tissues, lymph node and visceral metastases were 95.8%, 74.6%, 60.9% and 57.5%. S100A4 expression in associated cases was 43.6%, 71.8%, 70.3% and 90.0%, respectively. Significant differences in KiSS-1 expression was signifi- cantly higher in normal tissues than that in primary tumor tissues (P <0.001). While significant differences of S100A4 expression could be seen between normal (P <0.001) and between visceral and primary tumors (P <0.05). Conclusion: Tumor metastasis results from gradual accumulation of abnormal genetic alterations. Down-regulation of KiSS-1 and up-regula tion of S100A4 play a critical role in metastasis of gastric carcinoma