Serial sectioning combined with microscopy provides high resolution volumetric data to complement in-vivo imaging modalities and aid ex-vivo diagnostics. We describe the design of a fully-automated cryomicrotome combined with a multispectral reflection and fluorescence imaging system that enables high-throughput analyses of biological specimens with a large field of view and cellular resolution while keeping the manufacturing and running costs low. We show the performance of the system for representative applications in high-resolution volumetric imaging of reporter animals and multispectral tissue analysis. Furthermore, we demonstrate the versatility of the economical imaging system in applications such as in vivo epifluorescence imaging, histology slide scanning, cell counting and gel electrophoresis documentation.