Detecting clonal T-cell receptor (TCR)-gamma gene rearrangements (GRs) is an important adjunct test for diagnosing 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-gamma GR. The combination of TCR-beta, mono-V TCR-gamma and multi-V TCR-gamma detected more clonal cases (68/144, 47%) than any individual PCR assay. We detected clonal TCR-beta GR in 47/68 (69%) cases. Using either mono-V or multi-V TCR-gamma primers, the sensitivities for detecting clonality were 52/68 (76%) or 51/68 (75%). Using both mono-V and multi-V TCR-gamma primers improved the sensitivity for detecting clonality, 60/68 (88%). Combining either mono-V or multi-V TCR-gamma primers with TCR-beta primers also improved the sensitivity, 64/68 (94%). Significantly, TCR-gamma 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.