Fluorescence imaging targeting αvβ3 integrin demonstrated 93% sensitivity and 77% specificity at a cutoff score of 5 for distinguishing benign moles from high-grade dysplastic nevi and melanomas across 240 suspicious lesions. The technology achieved an area under the ROC curve of 0.907, with higher specificity (91%) possible at slightly reduced sensitivity (87%) using a more conservative threshold. This molecular approach represents a significant advancement beyond traditional visual assessment methods that rely primarily on morphological changes. Current melanoma screening depends heavily on dermatologists' clinical judgment and often requires tissue biopsies for definitive diagnosis, creating patient anxiety and healthcare costs. The ability to non-invasively detect integrin markers associated with malignant transformation could substantially reduce unnecessary biopsies while maintaining high sensitivity for cancer detection. However, this single-arm validation study across six clinics requires broader replication and cost-effectiveness analysis before widespread adoption. The technology's performance in community settings versus academic centers, and its integration with existing dermoscopy tools, will determine its practical clinical utility for the millions of Americans evaluated annually for suspicious skin lesions.