Since the progression and metastasis of solid tumors depend on their local microcirculation, we sought to characterize the tumor angiogenesis three-dimensionally in a highly metastatic mouse melanoma model, B16BL6 melanoma injected with Matrigel into syngeneic C57BL/6 mice by using confocal laser scanning microscopy and transmission electron microscopy. We found that B16 melanoma within Matrigel grew significantly quicker than B16 melanoma alone and was accompanied by altered tumor angiogenesis and avascular area. We characterized the unique patterns of avascular area by using confocal laser-scanning microscopy and transmission electron microscopy.