Diffuse large B cell lymphoma (DLBCL) is a heterogeneous disease with various morphological and molecular subtypes. It commonly occurs in the elderly as well as in people infected with HIV. According to the Hans' algorithm DLBCL can be classified prognostically into the favourable germinal centre (GC) subtype and the unfavourable non-GC subtype. The disease tends to be more aggressive in HIV infected individuals. Research on DLBCL has been largely conducted on HIV negative samples and it is still unclear how HIV affects the molecular mechanisms of the disease. We conducted a study to compare the expression levels of miR-21 in HIV negative and HIV positive DLBCL patients. Our results suggest that miR-21 expression levels are higher in HIV positive cases of DLBCL. We did not observe any statistically significant difference in miR-21 levels between DLBCL subtypes in both HIV negative and positive cases. Favourable prognosis in HIV negative patients was associated with high miR-21 expression and the reverse was true in HIV positive patients. In conclusion, our results indicate that HIV infection may affect the expression of miR-21 in DLBCL. This highlights the need for further studies on HIV positive DLBCL as the prognostic significance of miR-21 expression level may differ depending on the HIV status.