This study established that human cancer cells (A375 melanoma, HT-29 colon cancer, PC-3p prostate cancer) that were xenografted into suckling opossums could proliferate and globally metastasize as early as 11 days after injection. Light and electron microscopic examinations (HT-29 colon cancer) determined that the cellular features exhibited by the xenogeneic human tumors grown in laboratory opossums were consistent with those observed in tumors removed from humans. The tumor induction rate, patterns of tumor growth and regression, and types of host immune responses against the xenografted tumors were influenced by injection dosages, injection sites and injection ages of suckling opossums. The results highlight the value of the opossum model as a natural in vivo system for investigating human cancer growth, metastasis and apoptosis at the cellular and molecular levels; enhancing identification of tumor associated antigens or T cell epitopes through use of humoral and cellular expression cloning techniques; elucidating mechanisms utilized by tumor cells to evade host immunosurveillance; and devising diagnostic and therapeutic methods for cancer treatment.