Molecular analysis of paired tumours highlights the limitations of the current clinical criteria for identifying second primary tumours. At present the finding of identical novel microsatellite alleles in paired lesions provides a "gold standard" marker for establishing clonal origin. However, these aberrations occur at low frequency and other methods for determining clonality have been proposed. In the present study we have applied 3 molecular tests to establish whether it is possible to combine the results obtained with the different approaches to provide information about the likely origin of a second tumour when novel alleles are not found. Our findings provide substantive molecular evidence that a proportion of second tumours are recurrences of an index lesion and suggest that the finding of concordant allelic imbalance at two or more loci at two different chromosome arms together with concordant p53 mutations might provide a useful surrogate. We briefly review other published reports and emphasis the need to plan treatment to eliminate precursor lesions in the field rather than focusing on the visible primary lesion and the 1-2 cm of surrounding mucosa traditionally considered to be "at risk".