CLL is often discovered by chance when people have routine blood tests. Most of these people will have no symptoms at the time of diagnosis. CLL is suspected when blood tests reveal excessive numbers of lymphocytes. Excessive is defined by a number which can be reported in a variety of ways. There needs to be an absolute increase of lymphocytes, which is frequently seen in the complete blood count (CBC) report as either LY# or LY-ABS. Lymphocytes are said to be absolutely increased when the number is above 5.0 x 10 raised to the 9^th power per liter of blood or 5.0 x 10 raised to the 3^rd power in a microliter of blood. An older system would write this as 5,000 cells per microliter of blood, and many physicians still use this as it is easier to say. Most patients typically have more than two to three times this number of malignant lymphocytes at the time of their diagnosis.

Diagnosis is often confirmed via a bone marrow biopsy (BMB) or a blood test called flow cytometry. Other symptoms that may be present at diagnosis include fatigue, lack of energy, a general feeling of ill health, loss of appetite, enlarged lymph nodes, enlarged spleen, low-grade fever, weight loss, anemia, frequent infections, bruising/bleeding, bone or joint pain, and night sweats