Reed-Sternberg Cells: The diagnostic neoplastic cells of classic Hodgkin lymphoma (cHL) are Reed-Sternberg (RS) cells and variants. They are present in a mixed inflammatory background of eosinophils, neutrophils, mature lymphocytes, plasma cells, and histiocytes and make up only about 1% of the total cellular population in the involved lymph nodes or tissues. Classic RS cells are quite large measuring up to 100 microns in size with abundant pale eosinophilic or amphophilic cytoplasm. The nucleus is bilobed or multilobed making the cell appear binucleated or multinucleated in sections. Some RS cells may actually have two or more separate nuclei. The nuclei have a distinct, thick nuclear membrane and vesicular chromatin. There is a single, large, round, eosinophilic, viral inclusion-like central nucleolus surrounded by a halo. In the most classic examples of RS cells, the two nuclei, placed side-by-side created an "owl eye" appearance. Reed-Sternberg cells may be surrounded by a rosette of T-cells. Some cases show giant Reed-Sternberg cells with highly pleomorphic, hyperchromatic nuclei mimicking anaplastic carcinoma or a pleomorphic sarcoma. Reed-Sternberg-like cells may be present in other malignancies, including some non-Hodgkin lymphomas. Conversely, Hodgkin lymphoma can be diagnosed, in some cases, in the absence of classic bi-nucleated RS cells.