Lymph node (LN) metastasis is one of the most important risk factors for the prognosis of pancreatic cancer. This study aimed to identify novel LN metastasis-associated markers and therapeutic targets for pancreatic and gallbladder cancers. DNA microarray analysis was carried out to identify genes differentially expressed between 17 pancreatic cancer tissues with LN metastasis and 17 pancreatic cancer tissues without LN metastasis. The expression of LZIC, FXR, SCAMP1, and SULT1E1 is significantly higher in pancreatic cancer tissues with LN metastasis than in pancreatic cancer tissues without LN metastasis. We recently reported that FXR plays an important role in LN metastasis of pancreatic cancer, and in this study, we selected the secretory carrier membrane protein 1 (SCAMP1) gene. To determine that function of the SCAMP1 gene, we examined the effects of SCAMP1 knockdown on pancreatic and gallbladder cancer proliferation, migration, and invasion using SCAMP1 small interfering RNA (siRNA) and the activity of vascular endothelial growth factor (VEGF) was measured by enzyme-linked immunosorbent assay. SCAMP1 overexpression is associated with LN metastasis in pancreatic cancer patients. The siRNA-mediated downregulation of SCAMP1 resulted in a marked reduction in cell migration and invasion, but not proliferation in MIA-PaCa2, PANC-1, TGBC-1, and TGBC-2 cells. In addition, downregulation of SCAMP1 inhibited VEGF levels of conditioned medium from SCAMP1 siRNA-transfected cells. These results suggest that downregulation of SCAMP1 could be a potential therapeutic target for patients with pancreatic and gallbladder cancer.