Background: Cytological samples play a critical role in diagnosing advanced-stage tumors and those arising in difficult-to-reach anatomical sites such as the pancreatobiliary tract, lung, thyroid, suprarenal, pelvis, and others such as salivary glands. These samples are often the only available material for accurate diagnosis and for performing ancillary studies, such as immunocytochemistry (ICC) or the detection of molecular biomarkers. Summary: While the use of immunohistochemistry is well established and standardized on formalin-fixed-paraffin-embedded histological tissue, in cytological samples, it presents unique challenges. Methods used for obtaining and processing these specimens are complex and are not standardized among laboratories. Moreover, there is also diversity in the types of cytological samples potentially suitable for ICC. Key Messages: This review explores the current landscape of ICC practices in European and North American laboratories, highlighting variability in methods and the need for standardization to ensure reliable results and reproducibility of ICC on cytological specimens.

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