Recent data suggests the presence of cytotoxic (TIA-1 and granzyme B+) and regulatory T-cells (FOXP3+) in classical Hodgkin lymphoma (cHL) tissues has been shown to correlate with poor overall survival in mainly diagnostic biopsies. By tissue microarray analyses, we extend this observation to a cohort of relapsed/refractory cHL tissue biopsies and analyze immunohistochemical expression of FOXP3, TIA-1, and granzyme B in the inflammatory background and the tumor microenvironment. High expression of TIA-1 (>50%) correlated with poor overall survival (P<0.0001), low expression of FOXP3 (<25%) correlated with poor overall survival (P<0.01), and combined high TIA-1 (>50%) and low FOXP3 (<25%) correlated with poor overall survival (P<0.0001). Expression of cytotoxic and regulatory T-cells shows prognostic significance in the relapsed/refractory clinical setting of cHL.