Ultramicroscopy (also known as selective plane illumination microscopy, or SPIM) is a novel technique that allows optical sectioning and 3D reconstruction of large, centimeter sized, fluorescently labeled biological specimen with (sub)micrometer resolution. It is based on light sheet illumination and perpendicular fluorescence detection in biological specimen that are made transparent by a clearing procedure. This technique is very versatile and can be applied in any biological specimen. We have set up the first commercially available Ultramicroscope in Switzerland and adapted it to biological questions in immunology and neurobiology. The Ultramicroscope is uniquely suited for the investigation of rare immune cells during adaptive immune responses, and the anatomy of neuronal networks in whole brains. The Ultramicroscopy setup will form part of the “Microscopy Imaging Center” (MIC) platform already established at the University of Bern, thus being available to interested researchers inside and outside of the University of Bern.