Colorectal cancer is the second leading cause of cancer deaths in the United States. In 1995, there were about 160,000 new cases of colorectal cancers with 60,000 deaths resulting from the disease. One of the requirements for progress in understanding the etiology and improving the treatment of this disease is the development of new animal models in which normal tissue biology and all stages of carcinogenesis can be investigated. The tools are in place to prepare new mouse models for cancer research; what is needed is a dialog between basic and clinical researchers about the molecular biology of human tumors, their initiation and progression with respect to biological correlates and modeling in the laboratory mouse. To this end, The Jackson Laboratory has established a series of annual meetings and companion workshops on mouse models for studying human cancer with the overall goal of discussing the development and validation of preclinical mouse models and their use in translational cancer research. This series was designed to support the """"""""Mouse Models of Human Cancer Consortium"""""""" (MMHCC) RFA CA-98-013 released by NCI on July 29, 1998. The first meeting, held in October of 1999, focused on mammary cancer and the use of mouse models in preclinical research. Subsequent meetings highlighting the latest in modeling human cancer in mice focused on colorectal cancer (2000), prostate cancer (2001), preclinical trials (2002) and lung cancer (2003). This application requests support for a sixth year in the series titled """"""""Modeling Human Colorectal Cancer in Mice"""""""" to be held at The Bar Harbor Club in Bar Harbor by Jackson Laboratory and The American Association for Cancer Research (AACR) on September 30 - October 3, 2004. The meeting will immediately follow a companion workshop """"""""Techniques for Modeling Human Colorectal Cancer in Mice"""""""". Students (16) from the workshop will be invited to attend the meeting free of charge. Active investigators and students from around the world will have an opportunity to share ideas, establish new collaborations, discuss current progress and chart future directions in the biological analysis of the intestinal epithelium and its neoplasms. ? ? ?