Non-invasive and high-resolution imaging of microvasculature is essential not only for the diagnosis and evaluation of certain dermatological conditions but also in preclinical research to understand the development and treatment outcome in skin diseases and tumors. In clinical dermatology, so far, examinations are conducted only through visual inspection or by using dermatoscopes or capillaroscopes which illuminate and optically magnify selected areas of the skin. However, these modalities provide only superficial 2D images without any information about deeper structures, limiting a precise evaluation of the disease progression. In the field of tumor research, especially when it comes to anti-angiogenic therapies directly targeting the tumor vascular network, new imaging modalities are of great interest. Until recently, an evaluation of detailed tumor vascular structures was only possible by using invasive procedures like skin window chambers or skin flap models with intravital microscopy within a small field of view. Other non-invasive modalities like MRI or fluorescence imaging are limited due to low spatial resolution. With the introduction of the novel imaging modality of raster-scanning optoacoustic mesoscopy (RSOM), the before-mentioned limitations can be overcome. By solely using the intrinsic optical properties of hemoglobin without any additional contrast agents, non-invasive, high-resolution 3D images of the vasculature can be generated, enabling a more detailed insight and more precise evaluation of vascular changes in all layers of the skin.