Pre-therapy CLL patients from US Intergroup trial E2997 were analyzed with single nucleotide polymorphism microarrays to detect acquired chromosomal anomalies. The four CLL-typical anomalies (11q-, +12, 13q- and 17p-) were found at expected frequencies. Acquired anomalies in other regions account for 70% of the total detected and their number per subject has a significant effect on progression-free survival after adjusting for the effects of 17p- (and other covariates). These results were compared with a previous study of >50,000 subjects from the GENEVA consortium of genome-wide association studies, which analyzed individuals with a variety of medical conditions and healthy controls. The percentage of individuals with acquired anomalies is vastly different between the two studies (GENEVA 0.8%; E2997 80%). The composition also differs, with GENEVA having a higher percentage of acquired uniparental disomies and a lower percentage of deletions. The four common CLL anomalies are among the most frequent in GENEVA subjects, some of whom may have CLL-precursor conditions or early stages of CLL. However, the patients from E2997 (and other studies of symptomatic CLL) have recurrent acquired anomalies that were not found in GENEVA subjects, thus identifying genomic changes that may be unique to symptomatic stages of CLL.