Human papillomaviruses have been widely implicated as important etiologic agents in various squamous cell carcinomas including oesophageal carcinoma. p53 mutant oncoprotein has also been implicated in various tumours. Immunohistochemical analysis was employed to detect the co-expression of HPV and p53 mutant protein in biopsy specimens of patients of cancer oesophagus as well as controls. This analysis revealed a significantly higher immunopositivity (63%) of E6 oncoprotein of HPV 16/18 in carcinoma of the oesophagus. Immunoexpression of E6 oncoprotein of HPV did not alter significantly the degree of differentiation of the tumour. Seventy-seven percent of cases of oesophageal carcinoma showed strong immuno-staining for mutant p53 protein. A higher percentage (89%) of tissues showed immunoexpression of mutant p53 protein in conjunction with E6 oncoprotein of HPV 16/18 indicating a selective degradation of key cellular protein of p53 having regulatory properties which in turn leads to uncontrolled cellular proliferation. Therefore, coexpression of oncoprotein E6 of HPV 16/18 and mutant p53 protein may be considered as a "high risk" factor for progression to oesophageal malignancy.