Cytology and biopsy are complementary diagnostic procedures with important differences in turnaround time, cost, invasiveness, and diagnostic accuracy.

Collection of samples for cytology is typically performed at less financial cost to the owner and often at less physical cost to the patient, who may be spared a general anesthetic and invasive surgical procedure. The turnaround time for diagnostic cytology is also quicker, with most biopsy submissions requiring at least four days for sample preparation. For clinicians who are competent at examining aspirated samples of basic lesions (e.g., lipoma, mast cell tumor, septic inflammation), cytology may be provided as a point-of-care test.

Biopsy, however, has the advantage of providing the pathologist with much more detailed diagnostic information by virtue of the tissue architecture and associated tissue responses contained within tissue specimens. For diagnosis of many neoplasms, tumor grading and prognostication can only be performed on biopsy samples. Additionally, sufficient tissue may be collected for ancillary testing such as immunohistochemistry and PCR-based methods.

Ultimately, the decision to collect samples for cytology or biopsy will be informed by the clinician's differential diagnoses, the specific requirements of the patient, and the preferences of the owner.