Practically speaking, that means that looking in the pelvis during surgery and removing it for microscopic examination is the only sure method of diagnosis. In the early stages of the disease before the pelvic exam begins to change very much, a careful and thorough history may be the most important clue to correct diagnosis. As the disease progresses it can create some very definite physical findings that can be noted by a physician who is looking for the disease and who has some experience in recognizing it. Ultrasound, CT, and MRI can give limited information about cysts, but not all women with endometriosis have cysts, and not all cysts are endometriosis. CA 125 levels in the blood are not a good indicator for endometriosis.
Surgery remains the only certain way to diagnose endometriosis.
The simple answer is, we don't know for sure. The oldest and most widely taught theory is that menstrual blood sometimes flows backwards into the pelvis. That is, instead of draining out of the body through the vagina, the theory holds that the menstrual fluid backs up the fallopian tubes and drips into the pelvis, where it attaches to any surface and establishes a blood supply. If Sampson's theory is correct, endometriosis is not possible until a girl's first period occurs. In the embryo, cells with the potential to mature multiple ways develop in the wrong way in the wrong location.