Background: Visual oral examination (VOE) is a conventional oral cancer screening method. This study aimed to evaluate the value of methylation marker to assist VOE in identifying oral epithelial dysplasia and oral squamous cell carcinoma (OED/OSCC) from non‐cancerous lesions in a real‐world situation. Methods: 201 patients with high‐risk personal habits who self‐perceived oral anomaly were VOE examined, ZNF582 methylation (ZNF582m) tested, and histologically diagnosed. Results: Among them, 132 patients (65.7%) were histologically diagnosed OED/OSCC. Using VOE, 56.1% OED/OSCC patients had possible oral cancer, whereas 37.7% non‐OED/OSCC patients had leukoplakia. ZNF582m‐positive was detected in 90.2% OED/OSCC patients and 44.9% non‐OED/OSCC patients. Various logistic regression models were postulated to evaluate the diagnostic performance of conventional VOE and new strategies using ZNF582m. ROC analysis and its corresponding C‐index demonstrated that either triage or co‐testing models of VOE and ZNF582m could improve diagnostic performance and discriminative abilities compared with the VOE only approach. Conclusions: In conclusion, methylation marker test shows equivalent performance to an experienced judgment by oral maxillofacial surgeons and plays a significantly supplementary role in increasing the efficacy in identifying oral malignant lesions. ZNF582m may be an especially important tool for family physicians or general dentists to properly diagnose suspicious oral lesions.