Although the treatment of Hodgkin lymphoma (HL) has been improved, distinguishing reliable prognostic biomarkers could better stratify patients for more effective treatment. We analyzed the prognostic relevance of CD68+ tumor-associated macrophages (TAMs) by immunohistochemical analysis at diagnosis and standard clinical parameters in 52 ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)-treated patients with advanced stage classical HL (cHL). Patients with >25% CD68+ TAMs compared to those with ≤25% had worse 5-year overall survival (45% vs. 77%, log-rank p = 0.019) and showed a trend toward shorter 5-year event-free survival (51% vs. 71%, log-rank p = 0.19). Additionally, no significant correlation with selected clinical features was found. Significantly shorter 5-year overall survival was associated with International Prognostic Score (IPS) >2, bulky disease, elevated erythrocyte sedimentation rate (log-rank test, p = 0.003, p = 0.049, p = 0.007, respectively). In multivariate analysis, increased CD68+TAMs, IPS >2, and bulky disease were identified as independent prognostic factors for overall survival (Cox multivariate model, p = 0.006, p = 0.007, p = 0.013, respectively). Tumor-associated macrophages represent a potential prognostic biomarker which could contribute to better risk stratification of patients with cHL.