A good experimental model for metastasis of human pancreatic cancer would be a valuable tool for the study of this process, which contributes significantly to morbidity and mortality. Models of experimental metastasis using injection of tumor cells into the portal or systemic circulation bypass some important steps of the metastatic process. We describe invasion and metastasis following orthotopic transplantation of human pancreatic carcinoma into nude mice. Tumor pieces were used as xenografts in this study, and metastases were observed in the regional lymph nodes, liver, lungs, and distant lymph nodes of the animals. Peritoneal implants and ascites were not observed in this study. Orthotopic transplantation of human pancreatic cancer in the nude mouse appears to be a promising model of spontaneous metastasis relevant to clinical reality.