The DNA methylation index (MI) is calculated as a percentage of methylated cytosines to cytosines. We established the DNA MI in 100 normal individuals ranging in age between 1 month and 94 years and found that the age-specific DNA MI can be calculated (4.00-0.0034 x age). We determined the DNA MI in 23 patients with CLL ranging from 47 to 90 years and compared the results with age-matched controls. Using Cox proportional hazard models for MI, adjusting for age and white blood cell count, only the DNA MI correlated with early clinical indications for systemic therapy (p=0.0038, HR=7.00, 95% CI: 1.90-26.20).