Doctors often detect monoclonal gammopathy during blood tests for another condition. Upon noticing the extra compound, the doctor will likely administer further tests to determine the exact amount of M-protein in the blood. To rule out other causes, doctors may suggest additional blood tests, imaging tests such as MRI or CT scans, urine tests, x-rays of the bones, or quantitative immunoglobulin tests. In some cases, they may perform a bone marrow biopsy—a procedure in which a small needle extracts a small amount of tissue for analysis. Such a procedure, however, is typically reserved for those who are at a higher risk of developing serious disease.

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