Toluidine blue (TB) has been shown to aid in the detection and diagnosis of oropharyngeal squamous cell carcinoma (OSCC) and oral premalignant lesions (OPLs). TB has been shown to enhance visualization of oral lesions and assist in identifying sites of increased risk of dysplastic/malignant change and promote biopsy. TB has been shown to identify lesions with molecular changes associated with risk of progression of OPLs to OSCC. A recent prospective longitudinal study showed TB retention in histologic benign lesions and lesions with mild dysplasia that are at increased risk of progression to cancer. Clinical trials show that TB is useful in identifying asymptomatic OSCC and premalignant lesions at risk of progressing to SCC, which might otherwise be undetected until lesions become more advanced. The data supports TB use in oral examination of patients at risk of OSCC.