A new fast method is presented for the quantification of patient set-up errors during radiotherapy with external photon beams. The set-up errors are described as deviations in relative position and orientation of specified anatomical structures relative to specified field shaping devices. These deviations are determined from parameters of the image transformations that make their features in a portal image align with the corresponding features in a simulator image. Knowledge of some set-up parameters during treatment simulation is required. The method does not require accurate knowledge about the position of the portal imaging device as long as the positions of some of the field shaping devices are verified independently during treatment. By applying this method, deviations in a pelvic phantom set-up can be measured with a precision of 2 mm within 1 minute. Theoretical considerations and experiments have shown that the method is not applicable when there are out-of-plane rotations larger than 2 degrees or translations larger than 1 cm. Inter-observer variability proved to be a source of large systematic errors, which could be reduced by offering a precise protocol for the feature alignment.