Post-transplant lymphoproliferative disorders (PTLD) are emergent complications of organ transplantation occurring in 2% to 10% of transplanted patients. Epstein-Barr virus (EBV) infections are considered the most important factors for the development of these heterogeneous disorders. Primary effusion lymphoma (PEL) is a lymphoproliferative disorder predominantly described in patients with advanced AIDS and it is almost universally associated with human herpesvirus 8 (HHV8). In rare case, PEL also occurs in HHV8-negative patient, in the setting of hepatitis B and C virus infection. However, all these cases showed pan B-cell markers to be positive. Here, we report a case of PTLD presented as HHV8 negative and HIV-negative primary effusion lymphoma lacking near all lymphoid markers except PAX5 on immunohistochemistry, which created a diagnostic challenge. The diagnosis requires multiple approaches including molecular and genetic tests.