Polymerase chain reaction (PCR) was used to amplify the DNA fragments of the framework 3 region (FR3) of the immunoglobulin heavy (IgH) chain genes, from the tissue of 66 patients with B-lymphoproliferative diseases and 74 patients with other malignant diseases, reactive or normal tissue. The assay performed with 77% sensitivity, 100% specificity and 89% efficacy. In addition, the PCR assay cost less than 25% of the cost performing Southern blot analysis of tumor DNA, which has been the test performed to date, and had a turn around time of 24 hrs rather than the 7-14 days required to obtain a result from Southern blot analysis. These results suggest that PCR analysis of B-cell lymphoproliferative disease is superior to Southern blot analysis, in the setting of a diagnostic laboratory.