With a nitrosamine induced hamster pancreatic cancer cell line (HaP-T1), survival time and metastatic rates were compared between orthotopic cell implantation (OCI; n = 5) and orthotopic tissue implantation (OTI; n = 5) models. All the tumors were palpable (100% tumor take) after 1 week in both groups. Hamsters in the OCI group survived 71 +/- 2.17 days (range, 69-75 days), and in the OTI group, 73.8 +/- 4.03 days (range, 58-80 days). After necropsy, spontaneous metastases were noted in 100% of the animals. Direct invasion to adjacent organs was observed in four animals, and liver metastases, in three in the OTI group, which were significantly higher compared with the OCI group. On the other hand, peritoneal dissemination was observed only in the OCI group. Other metastatic sites showed no significant difference between the groups. All the histologically noted metastases had K-ras point mutation confirmed by polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP) analysis. We conclude that the homologous OTI model may be more useful than the OCI model. The OTI model may contribute to the development of therapeutic strategies in the field of pancreatic cancer research because of the capacity for invasion to adjacent organs, higher liver metastatic rate, and similarity to the clinical picture of the disease.