Introduction: Breast density is an important independent risk factor for breast cancer and is negatively associated with diagnostic sensitivity of mammography. Measurement of breast density can be used to identify women at increased risk of developing breast cancer and those who would benefit from additional imaging. However, measurement techniques are generally subjective and do not reflect the true three-dimensional nature of the breast and its component tissues.Method: A semi-automated method for determining the volume of glandular tissue from digitised mammograms has been developed in Manchester. It requires a calibration device (stepwedge) to be imaged alongside the breast during mammography, with magnification markers on the compression paddle to accurately determine breast thickness. Improvements to the design of the stepwedge and markers have enabled the method to be applied to the screening population for the first time. 1,289 women had their volumetric breast density measured using this method and additionally completed a questionnaire on breast cancer risk factors.Results: The method has demonstrated excellent intra- and inter-observer agreement. The median percentage breast density in the study cohort was 8.4% (interquartile range 4.9 - 14.2%). There was no significant difference between left and right breasts; the difference between MLO and CC views was significant (CC view was denser), but values were closely correlated (r = 0.92, p <0.001). The median glandular volume was 60.1cm3 and exhibited no significant variation between left/right breasts or CC/MLO views. A number of breast cancer risk factors were found to be significantly correlated with glandular volume and percentage breast density, including age, weight, BMI, parity, current HRT use and current smoking. The strength of correlation was equal to or greater than that of visually assessed mammographic density. Glandular volume and percentage breast density measurements demonstrated strong relationships with visually assessed mammographic density, which has been shown to be highly correlated with risk.Conclusions: These findings are promising and suggest that volumetric breast density measured using this method should be associated with breast cancer risk. However, further work is required to establish this relationship directly. The method will be used in a large study, known as PROCAS (Predicting Risk Of Cancer At Screening) which aims to develop individualised breast cancer risk prediction models; these have the potential to form the basis of tailored screening intervals. Preliminary work has been undertaken to adapt the method for full field digital mammography, which suggests that it is possible to use the integrated digital detector as the calibration device.