Structured light imaging (SLI) with high spatial frequency (HSF) illumination provides a method to amplify native tissue scatter contrast and better differentiate superficial tissues. This was investigated for margin analysis in breast-conserving surgery (BCS) and imaging gross clinical tissues from 70 BCS patients, and the SLI distinguishability was examined for six malignancy subtypes relative to three benign/normal breast tissue subtypes. Optical scattering images recovered were analyzed with five different color space representations of multispectral demodulated reflectance. Excluding rare combinations of invasive lobular carcinoma and fibrocystic disease, SLI was able to classify all subtypes of breast malignancy from surrounding benign tissues (p-value  <  0.05) based on scatter and color parameters. For color analysis, HSF illumination of the sample generated more statistically significant discrimination than regular uniform illumination. Pathological information about lesion subtype from a presurgical biopsy can inform the search for malignancy on the surfaces of specimens during BCS, motivating the focus on pairwise classification analysis. This SLI modality is of particular interest for its potential to differentiate tissue classes across a wide field-of-view (∼100  cm2) and for its ability to acquire images of macroscopic tissues rapidly but with microscopic-level sensitivity to structural and morphological tissue constituents.