Example methods and apparatus to perform multi-focal plane image acquisition and compression are disclosed. A disclosed example method includes capturing a first image of a portion of an object at a first focal plane and at a first resolution, computing a contrast metric for the captured first image, comparing the contrast metric to a threshold to determine whether to capture a second image of the portion of the object at the first focal plane and at a second resolution, wherein the second resolution is different from the first resolution, capturing the second image of the portion of the object at the first focal plane and at the second resolution, and storing a first representation of the second image in a file, the file containing a second representation of the portion of the object at a second focal plane, wherein the second representation is at the first resolution.
