The purpose of this study was to determine the significance of variables such as duration of the procedure, type of breast tissue, number of passes, depth of the biopsies, underlying pathology, the operator performing the procedure, and their effect on women's perception of pain and discomfort during stereotactic large-core needle breast biopsy. One hundred and fifty consecutive patients with a non-palpable suspicious mammographic lesions were included. Between three and nine 14-gauge breast passes were taken using a prone stereotactic table. Following the biopsy procedure, patients were asked to complete a questionnaire. There was no discomfort in lying on the prone table. There is no relation between type of breast lesion and pain, underlying pathology and pain and performing operator and pain. The type of breast tissue is correlated with pain experienced from biopsy (P = 0.0001). We found out that patients with dense breast tissue complain of more pain from biopsy than patients with more involution of breast tissue. The depth of the biopsy correlates with pain from biopsy (P = 0.0028). Deep lesions are more painful than superficial ones. There is a correlation between the number of passes and pain in the neck (P = 0.0188) and shoulder (P = 0.0366). The duration of the procedure is correlated with pain experienced in the neck (P = 0.0116) but not with pain experienced from biopsy.