Plasmablastic lymphoma (PBL) is a challenging diagnosis given its rarity and lack of expression of markers that are usually used by pathologists in establishing hematopoietic lineage. However, knowledge of the characteristic clinical setting, sites of involvement, and morphologic features of plasmablastic lymphoma can aid in the correct diagnosis of a suspected large cell lymphoma that is negative for B-cell- and T-cell-specific antigens. Herein, we review the clinical and pathologic features of plasmablastic lymphoma with an emphasis on the differential diagnosis of hematolymphoid neoplasms with immunoblastic morphology and/or evidence of plasmacytic differentiation by immunophenotype.