A whole organ or a whole lump is removed or excised. These are less common now, since the development of fine needle aspiration (see below). Some types of tumors (such as lymphoma, a cancer of the lymphocyte blood cells) have to be examined whole to allow an accurate diagnosis, so enlarged lymph nodes are good candidates for excisional biopsies. Some surgeons prefer excisional biopsies of most breast lumps to ensure the greatest diagnostic accuracy. Some organs, such as the spleen, are dangerous to cut into without removing the whole organ, so excisional biopsies are preferred for these.

Only a portion of the lump is removed surgically. This type of biopsy is most commonly used for tumors of the soft tissues (muscle, fat, connective tissue) to distinguish benign conditions from malignant soft tissue tumors, called sarcomas.

An endoscopic biopsy is probably the most commonly performed type of biopsy. It is done through a fiber-optic endoscope the doctor inserts into the gastrointestinal tract, urinary bladder, abdominal cavity, joint cavity, mid-portion of the chest, or trachea and bronchial system, either through a natural body orifice or a small surgical incision. The endoscopist can directly visualize an abnormal area on the lining of the organ in question and pinch off tiny bits of tissue with forceps attached to a long cable that runs inside the endoscope.

This is an extremely simple technique that has been used in Sweden for decades but has only been developed widely in the US over the last ten years. A needle no wider than that typically used to give routine injections is inserted into a lump or tumor, and a few tens to thousands of cells are drawn up (aspirated) into a syringe. These are smeared on a slide, stained, and examined under a microscope by the pathologist. A diagnosis can often be rendered in a few minutes. Tumors of deep, hard-to-get-to structures, pancreas, lung, and liver, for instance, are especially good candidates for FNA as the only other way to sample them is with major surgery. Such FNA procedures are typically done by a radiologist under guidance by ultrasound or computed tomography (CT scan) and require no anesthesia, not even local anesthesia. Thyroid lumps are also excellent candidates for FNA.