In vivo stains are the prompt resources, which have emerged in recent years so as to aid as clinical diagnostic tools in detecting early potentially malignant and malignant lesions. Toluidine blue by its property of retaining in the increased DNA and RNA cellular activity areas, aids in delineating the suspicious areas. However, it is hazardous if swallowed, and was shown to have toxicity to fibroblasts. Methylene blue has a similar chemical structure and exhibits similar physicochemical properties to toluidine blue. It is less toxic to the human body and has recently been proposed for screening some gastrointestinal or prostate tumors. The application of this material in detecting oral lesions has so far not been addressed. The objective of this study was to evaluate the sensitivity and reliability of in vivo staining with methylene blue as a diagnostic adjunct in screening for oral malignant or potentially malignant lesions. The present study involved the examination of seventy five patients suspected of having oral malignant or potentially malignant lesions by methylene blue staining.