QuantiFIRE is a versatile, quantitative, megapixel, 2k × 2k, cooled, monochrome digital camera with a 500% increase in field of view. It incorporates a patented, TEC-cooled system that develops noise-free images with an exposure time of up to 20 min. Multiple binning modes facilitate the acquisition of high-bit-depth monochrome images for quantitative image analysis. A simple yet powerful color merge function delivers brilliant color fluorescent images from the most challenging sample preparations.Applications for QuantiFIRE include a wide range of analytical photomicrography techniques, including monochrome fluorescence, quantitative live-cell imaging, FRET, FRAP, deconvolution and transmission electron microscopy. QuantiFIRE incorporates a four-megapixel CCD measuring 21.4 mm diagonally with 2048 × 2048 pixels that are 7.4 µm square, with a 40,000 electron-well depth -- the optimal size for low-light photomicrography imaging applications where increased sensitivity and dynamic range are important.