Surgical pathology is the most significant and time-consuming area of practice for most anatomical pathologists. Surgical pathology involves gross and microscopic examination of surgical specimens, as well as biopsies submitted by surgeons and non-surgeons such as general internists, medical subspecialists, dermatologists, and interventional radiologists.

The practice of surgical pathology allows for definitive diagnosis of disease (or lack thereof) in any case where tissue is surgically removed from a patient. This is usually performed by a combination of gross (i.e., macroscopic) and histologic (i.e., microscopic) examination of the tissue, and may involve evaluations of molecular properties of the tissue by immunohistochemistry or other laboratory tests.