Abstract An increase in high grade B-cell lymphomas has been noted in HIV infection. Sub-Saharan Africa is the epicentre of the epidemic and in Gauteng, South Africa >90% of patients with high grade lymphoma tested positive for HIV infection. The diagnosis of lymphoma may be challenging in HIV because of reactive conditions which mimic lymphomas, the atypical clinical presentation and the atypical histological findings. The WHO classification divides lymphomas into discrete categories. Despite this, tumours in HIV positive patients commonly show atypical morphological, immunophenotypic, molecular and cytogenetic features, making exact classification difficult. This has lead to an increase in the diagnosis of the highly aggressive B-cell lymphoma, unclassifiable with features intermediate between DLBCL and BL. It appears likely that HIV-associated lymphomas represent a continuum of disease.