Early identification of oral potentially malignant disorders (OPMD) remains a major clinical challenge. Point-of-care (PoC) salivary testing may provide a rapid, non-invasive adjunctive approach to support clinical decision-making. This case–control study included 42 participants: 21 patients with clinically and histologically confirmed OPMD and 21 healthy controls. Salivary p16 and EGFR were assessed using a point-of-care device, and their measurements were integrated with predefined clinical variables by the OraFusion software to generate a device-generated risk classification of low, moderate, or high risk. Among patients with OPMD, 57.14% were classified as high risk, 4.76% as moderate risk, and 38.10% as low risk, whereas 95.24% of controls were classified as low risk and 4.76% as moderate risk. Considering moderate and high device-generated risk classifications as positive test results, the assay achieved a sensitivity of 61.90% (95% CI, 38.44–81.89%) and a specificity of 95.24% (95% CI, 76.18–99.88%). These findings suggest that PoC salivary testing may provide valuable adjunctive information through a device-generated risk classification. However, its moderate sensitivity and the small, single-centre sample preclude its use as a substitute for histopathological diagnosis. Larger prospective, multicentre studies are needed to validate its clinical utility.