We recently identified a chronic lymphocytic leukemia (CLL) subgroup using the immunoglobulin variable heavy-chain (V_H) gene V_H3-21 with almost identical heavy-chain complementarity determining region 3s (HCDR3s) and preferential variable light-chain (V_L) gene usage, suggesting recognition of a common antigen epitope in this subset. To further explore the B-cell receptors (BCRs) in CLL, we characterized 407 V_H rearrangements amplified from 346 CLLs regarding V_H, diversity (D), and joining (J_H) gene usage and performed multiple alignment of the HCDR3 sequences. These analyses revealed 3 small subsets (2 V_H1-69 groups, 7 cases; and 1 V_H1-2 group, 5 cases) with highly restricted HCDR3 features including identical V_H/D/J_H usage, HCDR3 lengths, and shared N-sequences, in addition to the V_H3-21 group (22 cases). Furthermore, another 3 groups (9 V_H1-3⁺ cases, 3 V_H1-18⁺ cases, and 5 V_H4-39⁺ cases) had essentially identical V_H/D/J_H use and similar HCDR3 lengths but less conserved N-regions. Analysis in all 6 of these subgroups showed restriction in V_L gene use, whereas no association between V_H and V_L usage was found in cases without HCDR3 similarities. Altogether, structurally similar HCDR3s associated with preferential V_L gene usage implies selection of BCRs, especially in subsets showing high HCDR3 similarities, thus pointing to restricted antigen recognition sites and possibly involvement of specific antigens in CLL development.