Plasmablastic lymphoma (PbL) is a rare malignant disease characterized by an aggressive course, a difficult diagnosis, a diversity of clinical manifestations, and poor prognosis. To date, PbL is known to occur predominantly in males over the age of 40 and to be detected just at later stages, which sharply worsens the prognosis. There is the most pronounced association of this pathological condition with various immunodeficiency states, such as Epstein-Barr virus, human immunodeficiency virus (HIV), and herpes infections. In this regard, it is extremely important to make an accurate differential diagnosis of the disease on the basis of clinical, laboratory, morphological, and immunogenotypic updates. Considering that in 2008, PbL was defined by the World Health Organization as a separate group as diffuse large B-cell lymphoma with a plasmacytic phenotype, when there are rather small amounts of data, each described clinical case provides a unique opportunity to study variability in the manifestations of the disease, to determine the direction vector for the most effective therapeutic and preventive measures, and to assess the prognosis of the course of the disease.