The most prevalent BCL2 fusion in B-cell lymphoma involves the IGH gene, attributable to the t(14;18)(q32;q21) translocation; this chromosomal abnormality is predominantly observed in follicular lymphoma (FL) and serves as one of its diagnostic hallmarks. In contrast, the fusion of BCL2 with IGL via the t(18;22)(q21;q11) translocation occurs less frequently. To investigate the clinicopathological characteristics associated with t(18;22)/IGL::BCL2, we conducted an analysis of five cases of B-cell lymphoma exhibiting the t(18;22) translocation. These patients underwent comprehensive diagnostic assessments, including pathological examination, flow cytometry, karyotyping, fluorescence in situ hybridization (FISH) testing, and genome-wide mutation analysis. Simultaneously, we conducted a literature review. All five patients in the study were male and diagnosed with chronic lymphocytic leukemia (CLL). Two patients exhibited an isolated t(18;22) chromosomal abnormality, while the remaining three presented with an additional +12 abnormality. Genetic rearrangements involving BCL2 and IGL were observed in all patients. Immunophenotypic analysis revealed no significant differences between classical CLL and cases with the t(18;22)/IGL::BCL2 translocation. Genetic testing conducted on three patients confirmed the presence of IGHV mutations. Of the three patients for whom treatment information was available, one demonstrated treatment indications at the initial diagnosis, one demonstrated treatment indications 14 months later, both of them did not respond to the Bruton's tyrosine kinase (BTK) inhibitor, and another one did not meet criteria for treatment. A comprehensive literature review identified 51 cases of the t(18;22)(q21;q11) translocation, primarily associated with CLL diagnoses. Detailed clinical trajectories were available for seven patients, among whom four required treatments at initial diagnosis, and two exhibited resistance to BTK inhibitors. Based on our case series and literature review, these cases appeared to have shorter time to first treatment (TTFT); however, more studies are needed. The t(18;22) chromosomal translocation, resulting in IGL::BCL2 fusion, is an infrequent occurrence predominantly observed in cases of CLL. This genetic anomaly frequently coexists with trisomy 12. Preliminary data suggest that these cases may have a shorter TTFT, though larger cohorts are needed for validation.