Although tissue architecture cannot normally be seen in cytology specimens, the arrangement of cells can provide clues about the architecture of the tissue of origin. Cells may form papillary or acinar structures, flat sheets and 3D clusters.

Where cells appear crowded and disorganised within a cell sheet or group, this may be a clue to malignancy. Particular tumours may form characteristic structures that can be recognised e.g. papillae in papillary carcinomas.