No confirmed risk factors are known to predict Richter syndrome (RS), and the value of clinical prognosticators conventionally applied to chronic lymphocytic leukemia (CLL) is not firmly established in this setting. The objective of this study was to present evidence for RS in Chinese patients with CLL and risk factors for CLL transformation to Richter syndrome. With a median follow-up of 43 months from CLL diagnosis in 149 Chinese patients, 16 (10.7%) patients progressed to diffuse large B-cell lymphoma (DLBCL). According to correlation analysis, a high level of lactate dehydrogenase (LDH) and CD38 positivity were found to be independent predictors of transformation to RS. Survival analysis showed that presence of RS, advanced Binet stage, high level of LDH, high level of β(2)-microglobulin, high concentration of thymidine kinase (TK), ZAP-70 and CD38 expression, unmutated immunoglobulin heavy chain variable (IGHV) gene status and del(17p13) were adverse factors in determining overall survival (OS). Only del(17p13) was strongly associated with survival by multivariate Cox regression analysis. Median OS after transformation was 16 months (95% confidence interval, 5.6-26.4 months). The results support that RS is associated with a poor outcome, and a policy of close monitoring and careful biopsy is needed in patients carrying transformation risk factors.