We studied 123 lymph node biopsies from 99 patients with Hodgkin's disease, mixed cellularity type, with a high content of epithelioid cells (HDMCep), by light microscopy using conventional histologic and immunohistochemical techniques. The cellular composition and histologic structure, which are described in detail, serve as a basis for discriminating HDMCep from similar lymphomas with a high content of epithelioid cells, especially from lymphoepithelioid cell lymphoma (Lennert's lymphoma, LeL) and angioimmunoblastic (LgX) type of peripheral T-cell lymphoma with a high content of epithelioid cells (AILD-PTCLep). In all lymph nodes from patients with HDMCep, the nodal architecture was effaced. In 11% it was partially replaced by a massive infiltration of epithelioid cells and small to medium-sized lymphoid cells occurring in varying proportions with some immunoblasts. In all biopsy specimens, some typical Sternberg-Reed (SR) and Hodgkin (H) cells were found. Plasma cells and plasma cell precursors were present in all biopsy specimens; in most cases, they were sparse to moderate in number. Eosinophils were always present; half of the biopsy specimens had rather large numbers of them. Formation of granulomas like those seen in sarcoidosis was noted in 7% of the specimens. Increased vascularity and an increased number of fibers were found in 53% and 63% of the biopsy specimens, respectively. Necrosis was seen in 20% of the specimens. Immunohistochemically in 30 of 67 (45%) biopsy specimens, giant cells stained positively for the granulocyte-specific monoclonal antibody 3C4 (approximately CD15). Plasma cells and plasma cell precursors in all 70 specimens exhibited a polyclonal Ig pattern. A comparison of the main clinical and laboratory data in these three entities reveals both similarities and differences. HDMCep--defined as a special variant of Hodgkin's disease, mixed cellularity type (HDMC)--marks apparently the border between Hodgkin's disease and non-Hodgkin's lymphomas.