Background: Classical Hodgkin lymphoma (CHL) has a good response to treatment, however, approximately 20% of patients present refractoriness or recurrence. Current prognostic scales cannot accurately identify patients with worse prognosis. High macrophage frequency detected by CD68 expression associate with shorter progression-free survival (PFS) in CHL. However, there are no studies on CD163, a more specific marker for macrophages/M2 histiocytes. Aberrant T-cell antigens (TCA) expression in the Reed Sternberg cells (HRS) also correlates with shorter PFS and overall survival (OS). This encourages the identification of biomarkers that predict a poor response to treatment. Aims: To evaluate the frequency of the histiocyte marker CD163 and aberrant TCA expression of CD2, CD3 and CD4 in HRS cells, as well as their prognostic value in CHL. Methods: CHL cases were included from January 2009 to December 2015. Previous hematoxylin-eosin staining and immunohistochemical markers (CD30, CD15, CD20, CD3 and LMP1) were evaluated, then samples of 1 cm in diameter were taken with at least 10 HRS for Tissue microarrays (TMA), and immunohistochemical stains were performed for CD2, CD4, and CD163. Aberrant TCA expression was considered positive when one, two or the three T-cell markers were expressed on at least 20% of HRS cells, and the histiocyte marker CD163 was considered positive at 25% cutoff. Results: 433 CHL cases were diagnosed, 144 cases met the inclusion criteria and were analyzed. CD163 expression was observed in 66 cases while 78 cases were negative, finding correlations between CD163 and lymphopenia <600/mm3 (p = 0.05), serum albumin <3.4 g/dl (p = 0.003); advanced clinical stage (p = 0.002); and extranodal disease (p = 0.003). However, CD163 was not associated with shorter PFS or OS. Aberrant TCA expression in HRS cells was observed in 34 cases (23.6%), having a statistically significant correlation with nodular sclerosis subtype (p = 0.04); leukocytosis ≥ 15,000 / mm3 (p = 0.001); lymphocytosis> 600 / mm3 (p = 0.039); advanced clinical stage (p = 0.023); and tumor size> 10 cm (p = 0.051). Aberrant TCA expression was not associated with worse PFS or OS either. LMP1 expression co-occurred with Epstein Barr virus (EBV) in 59.6% of patients with mixed cellularity and 43.5% with nodular sclerosis subtypes respectively, in univariate analyses LMP1 expression was not associated with lower PFS (p = 0.30). In multivariate analyses, LMP1 expression was a protective factor for not having aberrant TCA expression with an odds ratio [OR] 0.3; 95% confidence interval [CI]: 0.12-0.78, but at the same time LMP1 correlated with high histiocyte frequency determined by CD163.Summary/Conclusion: In this study, the antigens CD163, CD2, CD3, CD4 and LMP1 were not prognostic biomarkers for PFS and OS, however, they can be useful to predict which patients will be more clinically compromised. Although there are few studies about the clinical correlation and aberrant TCA expression in CHL, in this study we observed a high percentage of aberrant TCA expression (23.6%) compared to previous reports (5-8%). Therefore, aberrant TCA expression in HRS cells is not an uncommon event in CHL; and should be distinguished from anaplastic large cell lymphoma, since this can impact treatment and prognosis.