Considering the enormous effort that has taken place over the years to discover new chemotherapeutic drugs for treating the common cancers, the conventional murine and xenograft test systems used to test efficacy for drug development have identified only a limited number of useful agents that are active clinically at well tolerated doses.During the last decade, considerable effort has been made to develop more clinically relevant and or predictive tumor models by the use of orthotopic transplantation of tumor material in rodents.It has been shown by several groups that it is possible to transplant/inoculate tumor material from a variety of tumor types (cell lines) into the appropriate anatomical site.Often these tumors will metastasize in a similar manner and to similar locations as the same tumor type will in human cancer.Interestingly as yet, although a body of literature has amassed on the technique itself and its implications for metastasis, there are relatively few laboratories or professional services using these test systems in drug development programs.The main question asked nowadays: Is the orthotopic tumor model actually more predictive than its subcutaneous counterparts? Indeed, some interesting observations being made on the role of the tumor site, vascularization and interaction with the stromal tissue on response to therapeutic agents especially for biologics.Therefore it is likely if done on highest quality level of surgery that the use of orthotopic systems will strengthen our ability to select the most appropriate molecules for recommended use in clinical studies.