Purpose: Elevated mammographic density (MD) is an independent risk factor for breast cancer (BC) as well as a source of masking in X-ray mammography.High-frequency longitudinal monitoring of MD could also be beneficial in hormonal BC prevention, where early MD changes herald the treatment's success. We present a novel approach to quantification of MD in breast tissue using single-sided portable NMR. Its development was motivated by the low cost of portable-NMR instrumentation, the suitability for measurements in vivo, and the absence of ionizing radiation. Methods: Five breast slices were obtained from three patients undergoing prophylactic mastectomy or breast reduction surgery. Carr-Purcell-Meiboom-Gill (CPMG) relaxation curves were measured from (1) regions of high and low MD (HMD and LMD, respectively) in the full breast slices; (2) the same regions excised from the full slices; and (3) excised samples after H 2 O-D 2 O replacement. T 2 distributions were reconstructed from the CPMG decays using inverse Laplace transform. Results: Two major peaks, identified as fat and water, were consistently observed in the T 2 distributions of HMD regions. The LMD T 2 distributions were dominated by the fat peak. The relative areas of the two peaks exhibited statistically significant (P < .005) differences between HMD and LMD regions, enabling their classification as HMD or LMD. The relative-area distributions exhibited no statistically significant differences between full slices and excised samples. Conclusion: T 2 -based portable-NMR analysis is a novel approach to MD quantification. The ability to quantify tissue composition, combined with the low cost of instrumentation, make this approach promising for clinical applications. 1200 | ALI et AL. K E Y W O R D S breast cancer, mammographic density, NMR-MOUSE, nuclear magnetic resonance, single-sided portable NMR, transverse spin relaxation time constant (T 2 )