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Cell--Cell Fusion Automatic Quantitation Cell–cell fusion is a highly regulated cellular event that is required in many biological processes such as fertilization and tissue development. The current challenge in this field is the identification of cell fusion catalyzing proteins and the determination of the mechanistic underpinnings of this process. Mating of haploid yeast cells provides a powerful model system to study cell–cell fusion and the development of techniques for high-throughput studies is key to the fusion machinery discovery process. Salzman and coworkers validated a FCM-based method that combines fluorescent surface staining of haploid cells and bimolecular fluorescence complementation (BiFC) to quantitatively assess cell–cell fusion efficiency in yeast mating mixtures. This method opens up the possibility of quickly getting accurate, robust, and reproducible data. Provided that durable and innocuous cell surface labeling and BiFC can be applied, this simple technique can be adapted to any other cell–cell fusion experimental models.