Background:　While　dynamic　contrast-enhanced　magnetic　resonance　imaging　(DCE　MRI)　is　recognized　as　the　most　sensitive　examination　for　breast　cancer　detection,　it　has　a　substantial　false　positive　rate　and　gadolinium　(Gd)　contrast　agents　are　not　universally　well　tolerated.　As　a　result,　alternatives　to　diagnosing　breast　cancer　based　on　endogenous　contrast　are　of　growing　interest.　In　this　study,　endogenous　near-infrared　spectral　tomography　(NIRST)　guided　by　T2　MRI　was　evaluated　to　explore　whether　the　combined　imaging　modality,　which　does　not　require　contrast　injection　or　involve　ionizing　radiation,　can　achieve　acceptable　diagnostic　performance.　Methods:　Twenty-four　subjects-16　with　pathologically　confirmed　malignancy　and　8　with　benign　abnormalities-were　simultaneously　imaged　with　MRI　and　NIRST　prior　to　definitive　pathological　diagnosis.　MRIs　were　evaluated　independently　by　three　breast　radiologists　blinded　to　the　pathological　results.　Optical　image　reconstructions　were　constrained　by　grayscale　values　in　the　T2　MRI.　MRI　and　NIRST　images　were　used,　alone　and　in　combination,　to　estimate　the　diagnostic　performance　of　the　data.　Outcomes　were　compared　to　DCE　results.　Results:　Sensitivity,　specificity,　accuracy,　and　area　under　the　curve　(AUC)　of　noncontrast　MRI　when　combined　with　T2-guided　NIRST　were　94%,　100%,　96%,　and　0.95,　respectively,　whereas　these　values　were　94%,　63%,　88%,　and　0.81　for　DCE　MRI　alone,　and　88%,　88%,　88%,　and　0.94　when　DCE-guided　NIRST　was　added.　Conclusion:　In　this　study,　the　overall　accuracy　of　imaging　diagnosis　improved　to　96%　when　T2-guided　NIRST　was　added　to　noncontrast　MRI　alone,　relative　to　88%　for　DCE　MRI,　suggesting　that　similar　or　better　diagnostic　accuracy　can　be　achieved　without　requiring　a　contrast　agent.