Oral submucous fibrosis (OSMF) is a chronic impairing disease of oral and oropharyngeal mucosa which was historically described by Pindborg and Sirsat in 1966 as “an insidious chronic disease affecting any part of the oral cavity and sometimes pharynx. Although occasionally preceded by and/or associated with vesicle formation, it is always associated with juxta-epithelial inflammatory reaction followed by fibroblastic changes in the lamina propria, with epithelial atrophy leading to stiffness of the oral mucosa causing trismus and difficulty in eating.” The oral manifestations include symptoms like burning sensation, blanching and leathery texture of the oral mucosa, submucosal fibrous bands, gradual reduction of mouth opening, reduced movement and depapillation of the tongue, and shrunken uvula It is mostly related with the areca nut chewing habit, which is consumed in different types of formulations by 10–20% of the World’s population. According to world Health Organization OSMF affected more than 5 million people all around the world. In Indian population the prevalence rate has changed from 0.03% to 6.4% in last four decades . Oral submucous fibrosis is one of the most common oral potentially malignant disorders, with nearly 4% rate of transformation into oral squamous cell carcinoma. To judge the severity of the disease, various researchers proposed several classifications based on clinical and histological features, based on various aspects of OSMF. Squamous cell carcinoma is defined as “a malignant epithelial neoplasm exhibiting squamous differentiation as characterized by the formation of keratin and/or the presence of intercellular bridges”. Studies suggest that in India, that many oral cancers are diagnosed in advanced stages due to insufficient approach toward disease leading to 60 to 80% of mortality rate. There is difference in clinical presentations of Oral submucous fibrosis and Oral squamous cell carcinoma and most of the oral cancers are asymptomatic in preliminary stages. There is greater probability of misdiagnosis when OSMF undergoing malignant transformation . Also lack of awareness amongst general practitioners causes failure to refer the patients for investigations, leading to diagnostic delay. Hence, early diagnosis and treatment of carcinoma is the key in improving the survival rates. In presence of various confounding factors like overlapping of clinical features, difficulty in assessment of OSMF patients of advanced stages and post operative healing complications, makes it challenging for the screening and staging of OSMF patients. As this disease carries high risk of malignant transformation, the early screening and clinical staging of OSMF is necessary for the risk assessment of the carcinomatous changes. Therefore, the efficacy of minimally invasive screening techniques should be tested. Some of these includes cytological, biochemical, histopathological, and optical diagnostic methods. In addition to these methods, Biocrystallization test is one such physical test that utilizes the phenomenon of morphogenetic forces. In this salt of cupric chloride is used to test quality of the substance without interacting with the test substance itself, resulting in slow crystallization. These slow growing crystals takes the form of different patterns, that can be studied for determining the quality of the test substance. Pfeiffer and Steiner introduced this sensitive crystallization technique in 1938 which is blood-based qualitative method. They conducted an experiment by adding cupric chloride (CuCl2) solution to diluted hemolyzed human blood of cancer patients . This colloidal solutions mixture gave rise to organic and inorganic salts that created various crystallization patterns due to different rates and amplitudes of molecular movements during evaporation . Thus, it was stated that hemolyzed blood containing colloidal proteins contributed to crystallization patterns. In other way, the concept of biocrystallization was based on the oxidative stress which is induced by the internal metabolic conditions. These crystallization forms appear to be “Transverse bar Formations” , “Muddle Formations” and “Hollow Glans Formations” patterns as peculiar findings in premalignancy and malignancy. To observe the changes in blood samples during routine hematological practice at early stage of carcinogenesis or even at the premalignant phase, such kind of diagnostic approach is need of hour in research. Pfeiffer crystallization method is simple, economical, dependable, less time-consuming and a minimally invasive method for early detection of cancer. This makes it more suitable for mass screening for premalignant and malignant lesions. In addition, this technique will help in early detection of cancer transforming lesion, that would ultimately help in enhancing the prognosis and increase the patient survival rate for individuals with an elevated risk or genetic predisposition. This shall potentially reduce the burden of cancer on patients and their families. Moreover, the healthcare systems can reach people from both rural and urban areas for early screening programs, that will in turn benefit the society to build up a healthy population, especially in developing countries. Hence, it can be used in correlation with the clinical and histopathological grading for the precancerous lesions where biopsy is infrequently recommended. Therefore, the current study aims to compare the patterns of crystallization and to further confirm the efficacy of crystallization test as a screening modality in Oral Submucous Fibrosis and Oral Squamous Cell Carcinoma.