Detecting clonal T-cell receptor (TCR)-␥ gene rearrangements (GRs) is an important adjunct test fordiagnosing T-cell lymphoma. We compared a recently described assay (BIOMED-2 protocol) , which targets multiple variable (V) gene segments in two polymerase chain reaction (PCR) reactions (multi-V) , with a frequently referenced assay that targets a single V gene segment in four separate PCR reactions (mono-V). A total of 144 consecutive clinical DNA samples were prospectively tested for T-cell clonality by PCR using laboratory-developed mono-V and commercial multi-V primer sets for TCR-␥ GR. The combination of TCR- , mono-V TCR-␥ and multi-V TCR-␥ detected more clonal cases (68/144 , 47%) than any individual PCR assay. We detected clonal TCR- GR in 47/68 (69%) cases. Using either mono-V or multi-V TCR-␥ primers , the sensitivities for detecting clonality were 52/68 (76%) or 51/68 (75%). Using both mono-V and multi-V TCR-␥ primers improved the sensitivity for detecting clonality , 60/68 (88%). Combining either mono-V or multi-V TCR-␥ primers with TCR- primers also improved the sensitivity , 64/68 (94%). Significantly , TCR-␥ V11 GRs could only be detected using the mono-V-PCR primers. We conclude that using more than one T-cell PCR assay can enhance the overall sensitivity for detecting T-cell clonality.