Nuclear factor kappa B (NF-kappaB) is one important pathway in T-cell proliferation and survival. In a previously reported microarray study, we found NF-kappaB pathway genes differentially expressed between peripheral (PTCL) and lymphoblastic lymphomas. Here, we investigated the expression of NF-kappaB pathway genes using cDNA microarrays in a group of 62 PTCL and in reactive lymph nodes. We found two different subgroups of PTCL based on the expression of NF-kappaB pathway genes. One-third of PTCL showed clearly reduced expression of NF-kappaB genes, while the other group was characterized by high expression of these genes. This distinction was found among all T-cell lymphoma categories analyzed (PTCL unspecified, angioimmunoblastic, cutaneous and natural killer/T lymphomas) with the exception of anaplastic lymphomas (ALCL), which were characterized by reduced NF-kappaB expression in anaplastic cells. Quantitative RT-PCR and immunohistochemical analysis of NF-kappaB-p65 protein confirmed these differences among PTCL subgroups. Importantly, we found that differentiation between NF-kappaB-positive and -negative PTCL could be of clinical interest. The expression profile associated to reduced expression of NF-kappaB genes was significantly associated with shorter survival of patients and seems to be an independent prognostic factor in a multivariate analysis.