Oral squamous cell carcinoma (OSCC) is characterized by cellular and subcellular alterations that are associated with a progression towards dedifferentiation and growth. There are several histologically distinct lesions of the oral cavity which have malignant potential. These are leukoplakia, erythroplakia, lichen planus, and submucous fibrosis. These are characterized by a spectrum of chromosomal, genetic, and molecular alterations that they share with each other as well as with the malignant lesions that develop from them. In this review we summarize the investigation of the molecular genetics of each of these lesions and relate them to the alterations, which have been demonstrated in OSCC, to define their location on the continuum of changes, which lead to malignant transformation.