Despite the huge research effort to improve the performance of the complementary metal oxide semiconductor (CMOS) image sensors, charge-coupled devices (CCDs) still dominate the cell biology-related conventional fluorescence microscopic imaging market where low or ultra-low noise imaging is required. A detailed comparison of the sensor specifications and performance is usually not provided by the manufacturers which leads the end users not to go out of the habitude and choose a CCD camera instead of a CMOS one. However, depending on the application, CMOS cameras, when empowered by image processing algorithms, can become cost-efficient solutions for conventional fluorescence microscopy. In this paper, we introduce an application-based comparative study between the default CCD camera of an inverted microscope (Nikon Ti-S Eclipse) and a custom-designed CMOS camera and apply efficient image processing algorithms to improve the performance of CMOS cameras. Quantum micro-bead samples (emitting fluorescence light at different intensity levels), breast cancer diagnostic tissue cell samples, and Caco-2 cell samples are imaged by both CMOS and CCD cameras. The results are provided to show the reliability of CMOS camera processed images and finally to be of assistance when scientists select their cameras for desired applications.