Cytological specimens, which are obtained by minimally invasive methods, are an excellent source of diagnostic material. Sometimes they are the only material available for diagnosis as well as for prognostic/predictive markers. When cytomorphology is not straightforward, ancillary tests may be required for a definitive diagnosis to guide clinical management. Immunocytochemistry (ICC) is the most common and practical ancillary tool used to reach a diagnosis when cytomorphology is equivocal, to differentiate entities with overlapping morphological features, and to determine the cell lineage and the site of origin of a metastatic neoplasm. Numerous immunomarkers are available, and some are expressed in multiple neoplasms. To rule out entities within a differential diagnosis, the use of more than one marker, sometimes panels, is necessary. ICC panels for diagnostic purposes should be customised based on the clinical context and cytomorphology, and the markers should be used judiciously to preserve material for additional tests for targeted therapies in the appropriate setting. This review offers a practical guide for the use of ICC for diagnostic cytopathology, covering the most commonly encountered non‐hematolymphoid diagnostic scenarios in various body sites.