A critical aspect in understanding and treating cancer progression and metastasis is the relationship of the host originating organ and metastatic "soil" organs that support the growth and progression of the cancer "seed". We have recently demonstrated that there is a great difference in seemingly similar visceral organs, the colon and the stomach to support the growth progression of transplanted human colon tumors in nude mice. To further understand the relationship of seed and soil in cancer, we transplanted the metastatic human colon tumor CO-3 on the liver of nude mice, which is a usual metastatic soil organ for this tumor if transplanted to the nude-mouse colon. The intrahepatically-transplanted CO-3 tumor grew extensively on the nude-mouse liver without intra-hepatic metastasis. However, cecal growth, peritoneal dissemination, and invasiveness were noted after extensive growth on the liver with no spread to other organs. This phenomenon suggested that the intra-hepatically transplanted tumor could "reversibly metastasize" to the orthotopic site and secondarily spread into the abdominal cavity. The observation reported here suggests that "seed" to "soil" is reversible in metastasis in that the tumor can spread in either direction between two "matched" organ "soil".