Although trophoblast cell surface antigen 2 (Trop2)-targeting drugs are already approved or under investigation in various solid tumors, the significance of Trop2 in lymphoma is unknown. Thus, our objective was to investigate the expression of Trop2 in diffuse large B-cell lymphoma (DLBCL) through a systemic immunohistochemistry screening. We constructed a tissue microarray comprising tissue from 92 DLBCL patients, each diagnosed at the University Medical Center Hamburg-Eppendorf (2020-2022). Trop2-immunohistochemistry was carried out, and positive staining was deemed a specific membranous positivity. Four samples were derived from Epstein-Barr virus (EBV)-positive DLBCL, with one case of EBV-positive DLBCL following angioimmunoblastic T-cell lymphoma (AITL). Strong Trop2 immunostaining was detectable in 1 of 91 analyzable samples, originating from a patient with a composite EBV-positive DLBCL emerging from AITL. Therefore, we performed an additional database search to identify all cases of composite EBV-positive DLBCL emerging from AITL since 2015. Five additional cases were identified and stained for Trop2, revealing two cases with strong B-blast positivity. Our preliminary data imply that Trop2 appears absent in de novo DLBCL, whereas Trop2 is strongly expressed in cases of a rare variant of EBV-positive DLBCL. Further investigations are needed to confirm our results, particularly on the subset of EBV-positive DLBCL emerging from AITL.