Neoplasms that are composed of large eosinophilic cells present a distinctive and challenging image to the diagnostic pathologist. Potential lineages for such lesions include several types of epithelial tissue, as well as melanocytic, lymphoid, germ-cell, and mesenchymal proliferations. Attention to morphological details represents a useful first step in the further evaluation of eosinophilic large-cell tumors. These tumors can usually be segregated into one of four cytological categories, including granular eosinophilic (oncocytic and oncocytoid), fibrillary eosinophilic (myoid), globular eosinophilic (rhabdoid and gemistocytic), and diffusely eosinophilic (hyaline-cell and deeply eosinophilic, not further specified). Correlation with anatomic locations, nuances of clinical presentation, and results of electron microscopic and immunohistochemical studies provides additional data that can be used for a specific interpretation, especially if it is applied in an algorithmic fashion.