Population-based oral cancer screening appears to be a promising health promotion strategy (especially in high-risk individuals) with significant increases in quality-adjusted life years saved. However, the current protocol, conventional visual inspection, and palpation of oral soft tissues for the early detection of pre-malignant or malignant changes, appears to be deficient. The adjunctive application of technology to highlight such lesions may increase the diagnostic yield. The purpose of this pilot study was to collect data, which might support the hypothesis that oral soft tissues exhibit features similar to the cervical epithelium following an acetic acid wash and visual inspection under chemiluminescent illumination. The data provides strong evidence to support the hypothesis. Epithelium with hyperkeratinization, hyperparakeratinization, and/or chronic inflammatory infiltrate reflects the diffuse, low-level, blue-white chemiluminescent light more strongly and appears amplified. Similarly, epithelium with an altered nuclear-cytoplasmic ratio also reflects the diffuse, low-level, blue-white chemiluminescent light. In such cases, the lesions become clinically discernible and appear "acetowhite." Large-scale studies are required to further refine issues related to the selectivity and specificity of the technology.