Identification of prognosticators for Binet A chronic lymphocytic leukemia is important for selecting patients with dismal prognosis. We analyzed CD49d expression in 140 consecutive Binet A chronic lymphocytic leukemia. At diagnosis, CD49d 30% (54/140, 38.6%) associated with proliferation markers, namely CD38 30% (p=3.9x10–6), LDH (p=0.007) and β2-microglobulin (p=0.020). Univariate log-rank analysis identified CD49d 30% as a risk factor of treatment free survival (p=8.3x10–5), time to progression to a more advanced stage (p=4.7x10–4), and time to lymphocyte doubling (p=0.009). Multivariate analysis selected CD49d 30% as an independent treatment free survival predictor after adjustment for biological (HR 2.28; 95% CI 1.71–4.45, p=0.015) and both biological and clinical variables analyzed together (HR 3.33, 95% CI 1.61–6.90, p=0.001). Within Binet A subgroups harboring favorable biological variables (IGHV homology <98%, favorable karyotype, CD38 <30%, ZAP70 <20%) or clinical variables, CD49d 30% consistently identified a subset of patients with short treatment free survival. Our observations indicate CD49d 30% as a new marker for the initial prognostic assessment of Binet A chronic lymphocytic leukemia.