High-performance smartphones, equipped with a digital camera and an application software, can render conventional bench-top laboratory instruments mobile at affordable costs. As the smartphone-based devices are portable and wireless, they have wide applications especially in providing point-of-care (POC) tests in resource-constrained areas. We developed a hand-held diagnostic system, Mobile SmartScope, which consists of a small optical unit integrated with a smartphone. The performance of the SmartScope was favorably compared with that of conventional light microscopy in detecting and quantifying red blood cells. We also evaluated the fluorescence detection limit of the SmartScope incorporated with a blue light-emitting diode and appropriate optical filters by using fluorescently labeled microbeads for intensity calibration.