SummaryClassical Hodgkin lymphoma (cHL) is characterized by a paucity of neoplastic Hodgkin/Reed Sternberg (HRS) cells within a complex cellular milieu that is rendered immunologically incapable of reacting against CD30 + HRS cells due to a plethora of immune escape mechanisms initiated by the neoplastic cells.Accounting for 25% of all lymphomas and nearly 95% of all Hodgkin lymphomas, patients with cHL are typically young adults. Besides traditional prognostic factors, such as the International Prognostic Index (IPI), newer imaging and ancillary biomarkers (CD68, Galectin-1 and plasma microRNA) have shown promise. Furthermore, the evolution of gene expression profiling (GEP) in recent years has enabled the development of several practically feasible GEP-based predictors with prognostic relevance. This review discusses the current status of clinical prognostication in cHL, the critical role of histological evaluation in light of several mimicking entities, and the relevance of tissue as well as serum biomarkers pertaining to immune escape mechanisms and recent GEP studies.Keywords: prognosis, classical Hodgkin lymphoma, immunohistochemistry, genome expression profiling, serum biomarkers, clinical risk factors.Since the seminal description 'on some morbid experiences of the absorbent glands and spleen' by Thomas Hodgkin in 1832 (Hodgkin, 1832), we have come a long way in our understanding of the pathobiology of the histologically peculiar and unique lesion identified as Hodgkin lymphoma (HL). The 20th century witnessed refined morphological descriptions and several classification systems for HL. As of today, the World Health Organization (WHO) 2008 classification (Swerdlow et al, 2008) recognizes four histological subtypes of classical HL (cHL): nodular sclerosis (NSCHL), mixed cellularity (MCCHL), the lymphocyte rich (LRCHL) and lymphocyte-depleted (LDCHL). Overall, the fundamental description of HL has largely remained unchanged through the past century. Despite the separation of nodular lymphocytepredominant HL (NLPHL) as a distinct entity in the late 1990s, it is critical to note that both cHL and NLPHL share a common biological origin from B-cells. The two major differences between them are (i) the presence of a relatively intact germinal centre/B-cell programme and (ii) lack of a role for Epstein-Barr virus (EBV) in the pathogenesis of NLPHL. In addition, these entities differ in their clinical features and behavior. The epidemiology of cHL is notable for complex interplay of genetic, racial and geographic as well immune competence/EBV-driven factors, which are instrumental in its pathogenesis (Swerdlow et al, 2008). Clinically, HL patients have been traditionally divided into two or three prognostic groups, mainly according to the stage and presence of systemic symptoms at diagnosis. The definition of these clinical and pathological prognostic groups varies, as does the choice of treatment. Prognostic factors are rarely studied clinically but are usually discovered when analysing data from reliable, large ...