The identification of minimal residual disease (MRD) in non-Hodgkin's malignant lymphoma is of immediate clinical relevance. Although several polymerase chain reaction (PCR)-based strategies are currently available, they all share serious technical or theoretic limitations with respect to their ability to detect the broad spectrum of mature B-cell neoplasia. We report a new strategy based on anchored PCR that does not rely on a particular chromosomal translocation or VH consensus sequence. It can yield the complete DNA sequence of the immunoglobulin heavy chain variable region (VHDJH). The assay is capable of detecting one neoplastic cell among 10(3)-10(4) normal cells with high specificity and has the potential to greatly expand the variety of B-cell malignant neoplasms that can be studied.