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The diagnosis of leukemia is made in dogs the same way it is in humans and most other animals. A blood sample is taken, and both a white blood cell differential count as well as a microscopic evaluation of the blood cells is done. If there is an increased number of a certain type of white blood cell, and/or there are many abnormal cells on the microscope slide, a diagnosis of leukemia (literally "white blood", but it is used to mean too many white blood cells in the blood) is made.

Further refinements of the diagnosis can be made by evaluating all available lymph nodes, taking chest radiographs and doing an abdominal ultrasound. There are also some histochemical tests that can be performed to classify the leukemia.

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