Spleen tyrosine kinase (Syk) expression was immunohistochemically examined in 250 gastric cancer patients. The rate of positive Syk expression was 42.4%. Syk expression was significantly associated with T1 tumors, lymphatic invasion, venous invasion and lymph node metastasis (P<0.0001). The 5-year survival rate was significantly higher among patients with nuclear Syk expression than among those who were negative for Syk expression (P=0.0003). However, Syk expression was not an independent prognostic factor. Loss of Syk expression was closely related to the malignant property of gastric cancer in the context of tumor depth and lymph node metastasis, especially in early gastric cancer.