Reed–Sternberg cells are distinctive, giant cells found with light microscopy in biopsies from individuals with Hodgkin lymphoma. They are usually derived from B lymphocytes, classically considered crippled germinal center B cells. In the vast majority of cases, the immunoglobulin genes of Reed-Sternberg cells have undergone both V(D)J recombination and somatic hypermutation, establishing an origin from a germinal center or postgerminal center B cell. Despite having the genetic signature of a B cell, the Reed-Sternberg cells of classical Hodgkin lymphoma fail to express most B-cell–specific genes, including the immunoglobulin genes. Reed–Sternberg cells are CD30 and CD15 positive, usually negative for CD20 and CD45. The presence of these cells is necessary in the diagnosis of Hodgkin lymphoma – the absence of Reed–Sternberg cells has very high negative predictive value. The presence of these cells is confirmed mainly by use of biomarkers in immunohistochemistry.