Objective: Impairment in cell-mediated immunity has long been recognized in classical Hodgkin’s lymphoma (cHL). The immunosuppressive environment at the tumor site and/or a primary T-cell defect may contribute to an ineffective immune clearance of Hodgkin/Reed-Sternberg (H/R-S) cells. Here, we analyzed whether circulating T lymphocytes of cHL patients show specific alterations in gene expression with possible impact on anti-tumor immunity. Material and Methods: Gene expression profiles were performed from CD3+ T cells isolated from peripheral blood samples of untreated patients with cHL versus two control groups consisting of healthy donors and patients with sarcoidosis. The regulation of gene expression was confirmed in additional patients for selected genes by real-time RT-PCR. Results and Conclusion: Circulating T cells of cHL show a Th1 immune response likely supporting anti-tumor immunity. However, the molecular profile reveals an association between cell cycle transition/proliferation and induction of immune regulatory genes which may limit an effective anti-tumor immune response of differentiated Th1 cells.