We previously compared time-domain diffuse optical spectroscopy (TD-DOS) with magnetic resonance imaging (MRI) using various water/lipid phantoms. However, it is difficult to conduct similar comparisons in the breast, because of measurement differences due to modality-dependent differences in posture. Dual-energy computed tomography (DECT) examination is performed in the same supine position as a TD-DOS measurement. Therefore, we first verified the accuracy of the measured fat fraction of fibroglandular tissue in the normal breast on DECT by comparing it with MRI in breast cancer patients (n = 28). Then, we compared lipid and water signals obtained in TD-DOS and DECT from normal and tumor-tissue regions (n = 16). The TD-DOS breast measurements were carried out using reflectance geometry with a source-detector separation of 3 cm. A semicircular region of interest (ROI), with a transverse diameter of 3 cm and a depth of 2 cm that included the breast surface, was set on the DECT image. Although the measurement area differed between the modalities, the correlation coefficients of lipid and water signals between TD-DOS and DECT were rs = 0.58 (p < 0.01) and rs = 0.90 (p < 0.01), respectively. These results indicate that TD-DOS captures the characteristics of the lipid and water contents of the breast.The validity of NIRS systems has generally been verified using tissue simulating phantoms such as intralipid-based aqueous phantoms [8,9] and resin-based hard phantoms [10], while phantoms with various lipid and water contents have been proposed in previous studies [11][12][13][14]. Merrit et al. and Ohmae et al. used such phantoms to compare lipid and water measurements between a diffuse optical spectroscopy (DOS) system and magnetic resonance imaging (MRI), which was defined as the "gold standard" technique [11,14]. In those studies, the authors confirmed that MRI and DOS measurements of water/lipid ratios in phantoms were almost identical. Studies using breast phantoms [13] and simulations [15] have also been conducted, but the structure of the living body is more complicated. Several studies have reported on the relationship between DOS parameters and breast density on MRI and their link with breast cancer risk [3,16,17]. Although previous studies have compared DOS with other modalities such as MRI, there have been no reports comparing DOS with other modalities in the direct measurement of lipid and water signals in the human breast. Although we previously compared lipid and water measurements of the contents of a phantom between MRI and time-domain diffuse optical spectroscopy (TD-DOS) [14], comparison of these parameters in living humans is difficult, because the measurement postures required in the two modalities differ: MRI measurement is conducted with the subject in a prone (downward facing) position, while the subject is generally in a supine (upward facing) or standing position for the DOS measurement.Computed tomography (CT) is a cross-sectional, high-resolution, three-dimensional diagnostic imaging modality ...