Alteration of expression of tumour suppressor genes and cell cycle regulators may be responsible for oral and pharyngeal cancer development. We have studied the expression of p53, pRb, cyclin D(1) and cdk4 in 53 cases of oral and pharyngeal squamous cell carcinomas using immunohistochemistry. Tumour expression of all nuclear proteins was scored according to the percentage of positive cancer nuclei. Positive p53 expression was detected in 27/53 (50.94%) cases. Lack of pRb immunostaining was observed in 39/53 (73.58%) cases. Overexpression of cyclin D(1) was shown in 21 (39.62%) tumours. The overexpression of cdk4 was detected in 43/53 (81.13%) cases. There was no significant association among these cell cycle regulatory proteins. This implies that the aberration of an important cell cycle regulator may be sufficient to disrupt regulatory mechanism in a manner favouring tumourigenesis. In summary, our results suggest that inappropriate expression of p53, pRb, cyclin D(1) or cdk4 is likely to contribute to the development of oral and pharyngeal cancers. The lack of pRb expression and/or overexpression of cdk4 play a crucial role in the development of this malignancy.