BACKGROUND: Stromal cell-derived factor (SDF)-1 and CXCR4 form an important chemokine ligand/receptor pair. Recent studies suggest that CXCR4 is expressed in certain cancer cells, and malignant cells use this chemokine/receptor system to promote tumor progression and metastasis. However, the pathophysiological significance of their expression in gastric cancer tissue has not been fully elucidated. PATIENTS AND METHODS: SDF-1 and CXCR4 expression levels in gastric cancer specimens obtained from 124 patients were examined by immunohistochemistry. RESULTS: The staining intensity of CXCR4 and SDF-1 in cancer cells was significantly higher in intestinal-type than in diffuse-type gastric cancer. There was a significant correlation between the expression of CXCR4 and SDF-1 and liver metastasis and lymphatic metastasis in the intestinal-type cancer; however, this correlation was not found in the diffuse-type cancer. Furthermore, intestinal-type cancer cells that permeated the vascular or lymphatic channels as well as liver and lymph node metastases showed strong CXCR4 and SDF-1 staining. CONCLUSION: The overexpressed CXCR4 and SDF-1 in intestinal-type cancer cells may be therapeutic targets for preventing lymphatic and hematogenous metastasis.