Cancer is a leading cause of mortality worldwide, and the number of new cases is projected to reach 22 million in the next two decades. Surgical resection of tissues is a standard of care for treatment of a variety of cancer patients. For the prostate, surgically removed tissues usually undergo a process of bread-loafing (cutting into 0.5-1.0 cm thickness), chemical fixation, embedding in paraffin (wax), sectioning (5-10 μm thick), staining, slide mounting and finally microscopic examination to determine whether all tumor growths have been excised. The procedure is labor-intensive, time-consuming and expensive. In addition, the majority of the prostate specimens are normal tissues that do not require detailed microscopic examination. These factors reveal the need to significantly accelerate the screening process and increase the efficient use of healthcare resources. Therefore, to reduce unnecessary processing time and costs, we proposed a fast and inexpensive imaging system to screen the surface of thick tissues for abnormality, before full histological processing. This system was designed to enable a wide imaging area and integrate deconvolution algorithms, which achieve high contrast and resolution. More specifically, the project was carried out in three phases: 1) design, construction, and optimization of a fluorescence microscope; 2) system calibration and optimization of deconvolution algorithms; and 3) system validation using fresh human tissues. The system is capable of generating a 1 x 1 cm2 image in a few minutes with 4 nm resolution. Success of such a system will facilitate clinical translation and increase efficiency of histopathological procedures, which are beneficial to both patients and healthcare providers.