Among patients undergoing stereotactic needle biopsy of the breast on a prone biopsy table, a substantial proportion of planned procedures are terminated prematurely. This study was undertaken to identify risk factors for cancellation of these procedures and to derive a clinical rule for predicting cancellation. Risk factors for cancellation were assessed in a group of 476 consecutive patients with non-palpable lesions planned for large core needle biopsy. 64 (13%) of these planned procedures were cancelled. Multivariate regression analysis was applied to identify independent risk factors for cancellation. Validation took place by applying the logistic rule on a validation set, including 5 cancelled and 35 successful biopsy procedures. Mammograms that were difficult to interpret owing to extremely dense breast tissue, axillary location of the non-palpable lesion, body mass index below 20, less than 15 mm distance from the lesion to the chest wall or the presence of more than one non-palpable lesion were identified as independent risk factors. The logistic rule discriminated patients with successful and cancelled biopsy procedures with a receiver operator characteristic (ROC) area of 0.72. In the validation set, the area under the ROC curve was 0.92. The prediction rule, based on mammographic and clinical findings, discriminated patients with successful and cancelled needle biopsy procedures to a certain extent. The risk of cancellation of the stereotacic biopsy procedure is considerable in cases of very dense breast tissue or the presence of multiple risk factors.