Characteristic components of Hodgkin lymphoma (HL) tissue are the mono- or multinucleated Hodgkin-Reed-Sternberg (HRS) cells. Given the challenges of isolating these rare malignant cells and the difficulty in culturing cells from patients, many investigators have tried to establish cell lines in efforts to develop cellular tools for in vitro studies. A limited number of HL cell lines exist and have provided valuable insights into HL pathobiology. A literature survey indicated that 35 cell lines derived from HL patients have been published. To determine whether all these alleged HL cell lines hold up to scrutiny, we examined the available data and also put some of these cell lines to the test of hierarchical clustering, providing additional information regarding assignment to cell line type and tissue derivation. Hierarchical clustering separated the bona fide (classical) HL cell lines completely from cell lines derived from other lymphoma categories and proved conclusively that HL cell lines represent a distinct entity, irrespective of the cellular origin of the HRS cells. We conclude by pointing out the need for an intensified search for new cell culture avenues in order to develop a new generation of informative HL cell lines covering more widely the spectrum of HL stages and subtypes.