The peripheral cannabinoid receptor (CB2) is mainly detected on B cells in the germinal centers (GCs) of the immune system, using an antibody directed against the extra cellular N-terminal domain of the receptor. We retrospectively investigated the CB2 receptor expression in diffuse large B-cell lymphomas (DLBCL) and its clinical relevance for treatment outcome.We have constructed a tissue micro-array (TMA) using lymphoma tissue of a large cohort of patients with DLBCL (N = 104) who were treated with CHOP. Forty-five out of 79 evaluable cases (57%) were CB2 positive. The expression of CB2 receptors was variably present in both the germinal center B cell (GCB) (n = 31) and the non-GCB/activated B-cell (ABC) (n = 43) DLBCL subtypes. CB2 positivity was not associated with a different outcome in this patient cohort (CR; P = 0.87, EFS; P = 0.32, DFS; P = 0.06 and OS; P = 0.18). Implementation of CB2 expression in the Hans algorithm using the markers CD10, BCL6, and MUM1 did not result in added prognostic value (all P-values >0.1).We hypothesize that although CB2 is normally expressed in GCs, the expression in one of the malignant counterparts such as DLBCL is aberrant. This may be an explanation for the absence of prognostic relevance for the expression of this protein.