© 2020 Elsevier Inc.Background: The programmed death receptor (PD-1) and ligand (PD-L1) pathway act by suppressing the antitumor response in chronic Hodgkin lymphoma (cHL). In this study, we aimed to investigate the effect of PD-1, PD-L1, and Epstein-Barr virus (EBV) positivity on prognosis at the initial diagnosis of cHL. Material and Methods: Thirty-six patients with cHL were retrospectively analyzed. PD-L1 staining was performed for RS cells and tumor microenvironment in the biopsy materials of cases. The presence of EBV was investigated by EBER (EBV-encoded RNA) method in tumor cell. P < .05 was accepted as significant. Results: The presence of advanced-stage disease, B symptoms, intermediate or high-risk international prognostic index (IPS), and extranodal involvement were found to be related to both PD-L1 positivity and EBV positivity in RS cells. PD-L1 positivity in RS cells was also associated with EBV positivity. There were 6 (16.7%) triple-positive (EBV+, RS-PD-L1+, mic-PD-1+) patients. All of these patients had advanced-stage disease, B symptoms at the time of diagnosis, and intermediate-high IPS score, and 4 of 6 patients had extranodal involvement. This group also had significantly shortened overall survival compared with others (38.4 months vs. 67.9 months P = .024). Conclusion: Our data suggest that there is correlation between PD-L1 positivity and EBV positivity in tumor RS cells that are also associated with extranodal involvement, intermediate and high IPS score, presence of B symptoms, and advanced-stage disease. In addition, we identified a group of triple-positive (EBV+, RS-PD-L1+, mic-PD-1+) cHL patients who have a very high-risk disease. © 2020 Elsevier Inc.We investigated the effect of PD-1, PD-L1, and EBV positivity on prognosis at the initial diagnosis of classic Hodgkin lymphoma. Our data suggest a correlation between PD-L1 positivity and EBV positivity in tumor RS cells, which are also associated with extranodal involvement, intermediate and high international prognostic index score, presence of B symptoms, and advanced-stage disease.