There is increasing attention to prevention as a means to reduce cancer incidence. Prevention interventions or therapies in turn rely on risk assessment programs to identify those women most likely to benefit from education and lifestyle changes. These programs are usually based either on interviews to identify ethnic, genetic, and lifestyle factors contributing to risk or on physical examination of the breast. For the latter it has been shown that the parenchymal density pattern observed in X-ray mammography can be used to assess an individual’s risk. Extensive areas of dense, glandular tissue that are relatively radio-opaque are associated with higher breast cancer risk, with an odds ratio of 4 to 6 compared with women in whom the breast density is low owing to an abundance of adipose tissue. Near-infrared optical transillumination spectroscopy has been used previously to investigate the physiological properties of breast tissue. In this study, women were recruited who underwent recently X-ray mammography. The tissue density was assessed by a radiologist. The women then underwent optical transillumination spectroscopy, for which an instrument was developed that delivered visible and near-infrared light to the breast. After being transmitted through the breast craniocaudally in one of four quadrants, the spectrum from 625 to 1050 nm was measured. The spectra were used as input to a Principal Component Analysis (PCA) that used the corresponding mammographic density as the reference standard. The study group consisted of 92 women aged 39 to 72 years. Without further stratification for age, menopausal status, or measurement position, the PCA numerical model predicted the radiological assessment of tissue density in the mid 80% to low 90%. © 2004 Society of Photo-Optical Instrumentation Engineers.