Oral neoplasm constitutes a predominant class of cancer that is encountered in South India. This is in large part due to the elevated risk of oncogenesis as a result of the habit of chewing of quids containing betel leaves, areca nut and smokeless tobacco. An array of molecular events are induced during the transformation of the buccal epithelium, among them the over-expression of oncogene products plays a key role. The c-Myc protein, a regulator of a number of key cellular signalling pathways, plays a pivotal role in a number of malignancies. The present study was undertaken to evaluate expression of the c-Myc protein in tumours of the oral cavity from the South Indian population, predominantly oral squamous cell carcinoma (OSCC). The c-Myc protein was over-expressed in 80% of the cases studied. Taking into account the pivotal role demonstrated for c-Myc in tumourigenesis, our observations suggest a key role for Myc oncoprotein in the genesis of OSCC as well as its potential as a therapeutic target in this population.