Until the mid 1990s, the majority of CLL patients were diagnosed once symptoms of the disease became noticeable. Today, the majority of patients are diagnosed through routine blood work as part of an annual physical exam or upon follow up of other medical conditions. Blood results reveal an elevated white blood cell (lymphocyte) count which should be followed up with more specific tests to confirm the diagnosis, as other diseases can also increase the lymphocyte count.

A diagnosis of CLL should be confirmed by an experienced hematopathologist who looks at the characteristics of the cells to evaluate proteins on the surface of the cells. CLL is diagnosed when there is expression of proteins CD5, CD19, CD20, and CD23. The next step is to stage the patients through examination of the lymph glands, liver and spleen. CAT scans are taken only if considered necessary by the doctor. Bone marrow aspiration and biopsy is not essential but is often useful in considering likelihood of progression.

The National Cancer Institute estimates that there will be 20,940 new cases of CLL in the U.S. in 2018 and that over 100,000 people are living with CLL in the U.S. The number of people affected by CLL grows every year due to the aging population and the fact that CLL patients can now live for many years. Survival has been prolonged as a result of an increase in knowledge and improved treatments.