Orthotopic transplantation of solid tumor fragments of human tumors in nude mice reproduces their pattern of local growth and distal dissemination. While lymphatic, hepatic or peritoneal dissemination can be reproduced, perineural invasion is absent. Early passages (less than 3) of xenografts show a high degree of stability regarding K-ras, p53 and p16 gene status. On the other hand, advanced passages of tumors acquire additional alterations in the p15 and Smad4 genes. Mutations in K-ras, p53, p15 and Smad4 genes can be acquired, in this model system, in the more advanced stages of pancreatic tumor dissemination. Finally, it is also possible to standardize local growth of these tumors as well as its dissemination pattern giving us a preclinical tool to evaluate the anticancer activity of new drugs.