We used 3'-minor groove binder (MGB) technology to develop consensus fluorogenically labeled probes of the immunoglobulin heavy-chain (IgH) gene for detecting minimal residual disease (MRD) in B-cell non-Hodgkin lymphoma (B-NHL). Sequence data from 59 patients with B-NHLs revealed a narrow consensus region as a result of somatic hypermutations and variable VH usage, indicating that it would be difficult to design ordinary non-MGB probes. MGB probes, characterized by shorter length but higher melting temperature, are more suitable for this situation than ordinary non-MGB probes. In fact, the present data indicated that about 20% more cases were detectable with MGB probes (34/59, 57.6%) than with the non-MGB probes (23/59, 39.0%) designed by Donovan et al. MGB technology is useful for the design of consensus fluorogenically labeled probes of the IgH gene for detecting MRD.