Among peripheral T-cell lymphomas (PTCL), the heterogeneous category of unspecified PTCL represents the most common subtype. Nevertheless, recurrent chromosomal translocations are unknown in this aggressive type of lymphoma. Here we describe a novel t (5; 9)(q33; q22) in unspecified PTCL. Molecular analyses delineated the breakpoints to ITK and SYK resulting in a previously undescribed expression of the Syk tyrosine kinase by Itk. ITK–SYK transcripts were detected in five of 30 (17%) unspecified PTCL, but not in cases of angioimmunoblastic T-cell lymphoma (n= 9) and anaplastic lymphoma kinase-negative anaplastic large-cell lymphoma (n= 7). In all five translocation-positive cases, the breakpoints were identical fusing the N-terminal pleckstrin homology domain and proline-rich region of ITK to the tyrosine kinase domain of SYK. Three of the five t (5; 9)(q33; q22)+ unspecified PTCL shared a very similar histological pattern with predominant involvement of lymphoid follicles and the same CD3+ CD5+ CD4+ bcl-6+ CD10+ immunophenotype. These results demonstrate the presence of a recurrent t (5; 9)(q33; q22) in a subset of unspecified PTCL, which may represent a novel distinct subgroup of PTCL.