While it is clear that there is an important role for the microenvironment in Hodgkin lymphoma (HL), the composition and functionality is still a matter of discussion. Both a Th2 and a Th1 phenotype has been described in classical HL (cHL), irrespective of the Epstein Barr virus (EBV) status of the tumor cells. A systematic comparison between cHL and nodular lymphocyte predominant HL (NLPHL) has not been performed before and studies on the composition of the cells in- versus outside of the tumor area are missing. We compared the composition of the microenvironment of 14 cHL (7 EBV+ and 7 EBV-) and 10 NLPHL suspensions by flowcytometry. CD26 expression was used to identify cells in- (CD26-) and outside (CD26+) the tumor cell area. Results: In EBV+ cHL there were more CD56+CD16+ NK cells, and more CD69+, Granzyme B+ and TIA-1+ CD8+ cells than in EBV- cHL. We saw no differences between EBV+ and EBV- cHL when looking at the location of the cells. Compared to cHL, NLPHL contained more PD-1+ CD4+ cells and PD-1+CD57+CD4+ cells, while cHL showed more CCR7+CD45RA+CD4+, FoxP3+CD4+, CD25+CD4+, CXCR5+ICOS+CD4+, CXCR3+CD8+ and CD56+ cells. In cHL, we found more CD69+CD4+ and FoxP3+CD4+ cells inside, and more CD25+CD8+ cells outside the tumor cell area. In NLPHL, the distribution of CD69+CD4+ cells and CD25+CD8+ cells was similar to cHL. In addition, we found more CD69+CD8+, and more PD1+CD4+ cells inside, and more FoxP3+CD25+CD4+ cells outside the tumor cell area. Both HL subtypes are characterized by high numbers of CD69+CD4+ cells inside the tumor cell area, and a shift of CD25+CD8+ cells from in- to outside the tumor cell area. Conclusions: PD-1+CD4+ T follicular helper cells normally provide help to germinal center B cells and the increase in the tumor cell area of NLPHL indicates a similar function for LP cells. In cHL, the increase of FoxP3+ T regulatory cells might provide an immune suppressive environment for the HRS cells. Both types of HL depend on different cells in the direct tumor cell environment, fitting the different nature of the tumor cells.