Objective: To investigate the Grb2 expression in pancreatic carcinoma and its clinical significance. Methods: The Grb2 gene and protein expressions in 6 types of pancreatic cancer cell lines were detected by real-time PCR and Western blot, respectively. The Grb2 protein expressions in pancreatic cancer tissues and their adjacent normal tissues from 80 cases were determined by tissue microarray technique, and the relations of Grb2 expression status with clinicopathologic profiles of the pancreatic cancer patients were analyzed. Results: Both the Grb2 mRNA and protein showed relatively high expression level in the highly invasive and poorly differentiated pancreatic cell lines PANC-1, MIA-PaCa-2 and AsPC-1, but presented relatively low expression level in the less invasive and well differentiated pancreatic cell lines BxPC-3, SW1990 and capan-2. The Grb2 expression was detected in all tested pancreatic cancer tissues, but no or weak Grb2 expression was found in their adjacent normal pancreatic tissues. Statistical analysis showed that high Grb2 expression was associated with poor differentiation of the tumor and lymph node or distant metastasis (both P<0.05). Conclusion: Grb2 expression is closely related to the degree of differentiation and ability of invasion and metastasis of pancreatic cancer, and high Grb2 expression may predict highly malignant tumor grades and poor outcome.