Peripheral T-cell lymphomas (PTCL) have a variable outcome. We have investigated the prognostic value of molecular staging in non-anaplastic PTCL. T-cell receptor gamma rearrangements were routinely determined in peripheral blood (n = 40) and bone marrow (n = 38) of patients with PTCL (75% unspecified) by conventional PCR at diagnosis. Tissue controls for PCR included 24 tumour biopsies. Twenty-four patients (60%) had a PCR-detectable clonal TCR gamma rearrangement in PB or BM. These TCR gamma PCR positive patients had significantly more stage IV disease (14 patients of 15 patients; P = 0.001), elevated LDH (14 of 18 patients; P = 0.04), higher IPI (16 of 21 patients; P = 0.03), more anemia (15 of 19 patients; P = 0.02) and lower platelet counts (seven of seven patients; P = 0.02). Clinical outcome of this clonal group was characterised by lower complete remission rates (37.5% vs. 62.5%), and overall response rates (58.3% vs. 87.5%; P < 0.05) as well as a significantly shorter median overall survival (12.8 vs. 30.0 months; P = 0.006). Patients with clinical stages I - III but molecular stage IV had an equally poor overall survival when compared with patients with clinical stage IV (15.8 vs. 13.9 months). In contrast, patients with CS I - III in the absence of a TCR gamma rearrangement in PB or BM had a favourable outcome with an estimated overall survival of 70% at 3 and 5 years. Molecular staging in PB and BM by TCR gamma PCR at diagnosis may serve as a useful prognostic tool in PTCL.