Peripheral T-cell lymphoma, unspecified (PTCLU) is the most common T-cell lymphoma variant. The molecular heterogeneity of PTCLU is reflected by a diverse clinical course. Several prognostic factors have been studied, but further refinement is needed. The aim of our study was to retrospectively evaluate the presence of lymphopenia, defined as a lymphocyte count of<1000 cells/mm, as a prognostic factor for survival in patients with PTCLU. Sixty-nine cases with a pathological diagnosis of PTCLU were included in our analysis. Lymphopenia was seen in 38 of the patients and was statistically associated with a worse response to chemotherapy. In univariate analysis, lymphopenia, IPI score>2, and Prognostic Index for PTCLU (PIT) score>2 were associated with a worse overall survival. In multivariate analysis, lymphopenia and a PIT score>2 were the only independent poor prognostic factors, implying an important role of the patient's immune system in both response to therapy and survival. © 2010 Informa UK, Ltd.