Clinically-relevant animal models of human cancer are greatly needed for the study of human cancer biology and the development of new cancer therapeutics and diagnostics. We report here that by orthotopically transplanting histologically-intact human colon cancer to the colon of the immunodeficient nude and scid mouse mutants that extensive local growth and liver metastases occur consistently even after extensive in vivo orthotopic passage. We demonstrate that the liver metastases arise by hematogenous spread. The models described in this report for human colon cancer should prove useful for individual cancer patients as well as for basic and applied studies to develop improved treatment.