B-cell chronic lymphocytic leukemia (CLL) is the most common type of adult leukemias in the Western countries, however, infrequent in the Eastern. A diagnosis of CLL requires a count of B-lymphocytes ≥5.0×109/L. Asymptomatic person with <5.0×109/L B-lymphocytes is defined as monoclonal B-cell lymphocytosis (MBL). To compare the clinical characteristics, prognostic factors, and outcome of Chinese patients with MBL and CLL, we present a study from our single centre of 20 patients with MBL and 136 patients with CLL. The factors included: age at diagnosis, gender, direct antiglobulin test (DAT), immunoglobulin heavy chain variable gene (IgHV) mutational status, ZAP-70 protein, CD38 expression level, and molecular cytogenetic aberrationswere analyzed in MBL and CLL subgroups. The Kaplan-Meier methodwas used to construct survival curves, and resultswere compared using the log-rank test. Patients in the MBL category were slightly older than in the CLL category. There was no significant difference of these clinical and biological characteristics between patients in MBL subgroup and early stage CLL (Binet A). The incidence of positive DAT was significantly increased in CLL patients at Binet B and C, compared with MBL (P=0.036). IgHV gene mutation in MBL is skewed, with more than 92.3% of subjects harbored mutated IgVH genes (P = 0.025). The proportion of MBL patients with a 13q14 deletion or trisomy 12 was similar to that of CLL patients. Moreover, markers associated with poor prognosis (deletion of 11q22 or 17p13) in these MBL populations were less than those in Binet B and C CLL patients (P=0.025). No statistically significant differences in ZAP-70 and CD38 status were observed between the MBL and CLL subgroups. During a median follow-up period of 45.5 months, MBL patients had a low probability of progression, with no patients transformed to aggressive non-Hodgkin’s lymphoma or dying of CLL-related causes. The overall survival of MBL was very similar to Binet A CLL, but longer than that of CLL patients at advanced stages (Binet B and C) (P=0.024). Our study demonstrated that a more indolent clinical course and superior clinical outcome for patients with MBL compared to CLL.