We have previously reported a comparison between edge-corrected near-infrared optical mammograms and those that have undergone a further image-processing step based on a spatial second derivative. In this work, we go a step further by combining the second-derivative images from four wavelengths (690, 750, 788, and 856 nm) to obtain oxygenation-index images. While the spatial second derivative improves contrast and allows for visibility of fine structures in the images, thereby improving the sensitivity to tumor detection, additional information is needed to avoid false-positive results. The oxygenation-index images are introduced to address this issue. Oxygenation information may help discriminate benign from malignant breast lesions, thereby effectively complementing single-wavelength optical mammograms that display optically dense regions within the breast with high sensitivity. © 2004 Society of Photo-Optical Instrumentation Engineers.