Angiogenesis is a central cancer hallmark, necessary for supporting tumor growth and metastasis. In vivo imaging of angiogenesis is commonly applied, to understand dynamic processes in cancer development and treatment strategies. However, most radiological modalities today assess angiogenesis based on indirect mechanisms, such as the rate of contrast enhancement after contrast agent administration. We studied the performance of raster-scan optoacoustic mesoscopy (RSOM), to directly reveal the vascular network supporting melanoma growth in vivo, at 50 MHz and 100 MHz, through several millimeters of tumor depth. After comparing the performance at each frequency, we recorded, for the first time, high-resolution images of melanin tumor vasculature development in vivo, over a period of several days. Image validation was provided by means of cryo-slice sections of the same tumor after sacrificing the mice. We show how optoacoustic (photoacoustic) mesoscopy reveals a potentially powerful look into tumor angiogenesis, with properties and features that are markedly different than other radiological modalities. This will facilitate a better understanding of tumor’s angiogenesis, and the evaluation of treatment strategies.