A core needle biopsy is a percutaneous ("through the skin") procedure that involves removing small samples of breast tissue using a hollow "core" needle.

The needle used in core needle biopsy (16 gauge) is larger than the one used in FNAC. The needle has a special cutting edge. The breast area is applied with local anesthesia after localizing the lump and by fixing the lesion with one hand and performing a freehand needle biopsy with the other. In the case of non-palpable lesions (those unable to be felt), stereotactic mammography or ultrasound image guidance is used.

The core needle biopsy procedure takes only a few minutes, and most patients are able to resume normal activity almost immediately afterwards. Core needle biopsy usually allows for a more accurate assessment of a breast mass than fine needle aspiration (if the sample is found to be solid or cloudy, suspicious-looking fluid) because the larger core needle usually removes enough tissue for the pathologist to evaluate abnormal cells in relation to the surrounding small sample of breast tissue taken in the specimen.

Core needle biopsy, like fine needle aspiration, only removes samples of a mass and not the entire area of concern. Therefore, it is possible that a more serious diagnosis may be missed by limiting the sampling of a lesion (abnormality).