Histopathological detection of metastases in dissected lymph nodes of cancer patients is critical to proper staging and management but current histological methods fail to detect small, but clinically-relevant, metastases. Quantitative ultrasound (QUS) permits characterization of tissue microstructure using system-independent estimates. In this study, more than 250 freshly-excised lymph nodes were evaluated using specifically designed QUS methods that demonstrated an ability to guide pathologists towards suspicious regions using an interactive and easy-to-use GUI called Lymph Explorer. Radio-frequency (RF) data were acquired in 3D using a 26-MHz transducer and RF data were processed to yield 13 QUS estimates associated with tissue microstructure. The 13 QUS estimates were combined using a linear discriminant classifier to derive cancer-probability estimates and classification performance was assessed using ROC methods. For gastrointestinal nodes, the areas under the ROC curves (AUCs) exceeded 0.95. Slightly poorer results (AUCs 0.85) were obtained for nodes of breast-cancer patients. Lymph Explorer can interactively display any three orthogonal cross-sectional B-mode images with overlaid color-coded cancer probabilities. In particular, Lymph Explorer permitted localization of small metastases in some partially-metastatic cases. The QUS approach integrated with Lymph Explorer potentially could drastically reduce the current rate of false-negative determinations by efficiently guiding pathologists to suspicious regions in dissected lymph nodes.