There is overlap between cytopathology and histopathology in performing a frozen section, which is the examination of tissue taken intra-operatively to give the surgeon a preliminary diagnosis whilst the surgery is still in progress. This may tell the surgeon, for example, that a suspicious mass is non-cancerous, allowing for more conservative surgery, or that a lymph node in the axilla (arm pit) contains cancer, requiring all of the axillary fat and lymph nodes to be surgically removed. Time is crucial in performing a frozen section, as the surgical team wants an answer as quickly as possible to reduce the amount of time for the patient to be under the general anaesthetic.

When a frozen section is performed, the histopathology laboratory will initially be notified that the surgical specimen is on its way from theatre, allowing time to prepare to receive the sample. The tissue will be examined on arrival by a pathologist, who describes and measures it before selecting the area of most interest to be processed (put onto a slide). Instead of the routine method of leaving the tissue in formalin to fix for a number of hours before cutting and staining it (see tissue preparation), it will be frozen using a cryostat or liquid nitrogen before sections are cut on a cooled microtome (cutting machine), mounted and stained by the medical scientist or anatomical pathologist. This reduces processing time from a day or two to 10 to 20 minutes. However, freezing results in some distortion of the tissue and a less satisfactory stain, making routine processing of tissue the preferred technique when tissue is submitted following a surgical procedure.

Another method which can be employed instead of freezing the tissue sent by the surgeon intra-operatively is of imprint smears. Here the tissue is cut and pressed or smeared onto a glass slide, then stained and examined under the microscope. This process leaves individual cells from the tissue on the slide and is therefore a cytopathology technique. Imprint smears further reduce the time taken to examine tissue and are most often used to check whether cancer has spread to involve a submitted lymph node (metastasis).