Whole-body imaging with fluorescent proteins has been shown to be a powerful technology to follow the dynamics of metastatic cancer. Whole-body imaging of fluorescent protein-expressing-cancer cells enables the facile determination of efficacy of candidate anti-tumor and anti-metastatic agents in mouse models. GFP-expressing transgenic mice transplanted with the RFP-expressing cancer cells enable the distinction of cancer and host cells and the efficacy of drugs on each type of cell. This is particularly useful for imaging tumor angiogenesis. Cancer-cell trafficking through the cardiovascular and lymphatic systems is the critical means of spread of cancer. The use of fluorescent proteins to differentially label cancer calls in the nucleus and cytoplasm and high-powered imaging technology are used to visualize the nuclear-cytoplasmic dynamics of cancer-cell trafficking in both blood vessels and lymphatic vessels in the live animal. This technology has furthered our understanding of the spread of cancer at the subcellular level in the live mouse. Fluorescent proteins thus enable both macro and micro imaging technology and thereby provide the basis for the new field of in vivo cell biology.