Traditional B-cell mitogens often fail to promote effective cell division in vitro for mature B-cell neoplasms, hindering chromosome analysis. The combination of DSP30 and IL-2 (DSP30/IL-2) has been suggested as a better alternative. This review evaluates DSP30/IL-2 efficiency using a systematic review and meta-analysis of 20 studies. Studies comparing the successful culture rate (SCR) and/or abnormalities detection rate (ADR) of DSP30/IL-2 against traditional mitogens and/or fluorescence in situ hybridization (FISH) were included. Subgroup analyses were performed for cases of chronic lymphocytic leukemia (CCL) and other B-cell neoplasms (OBCN). The findings show no significant difference in SCR between DSP30/IL-2 and traditional mitogens, but DSP30/IL-2 significantly increases ADR. However, DSP30/IL-2's ADR is lower than that of FISH. Analyses by CLL and OBCN subgroups showed similar results. Overall, DSP30/IL-2 is a superior alternative for cytogenetic studies in mature B-cell neoplasms.