BACKGROUND/AIMS Loss of function of the retinoblastoma (Rb) tumour suppressor gene, located on chromosome 13, is common in many inherited and sporadic forms of cancer. Inactivation of its gene product by oncogenic human papillomaviruses (HPV) plays a key role in the genesis of cervical cancer. It has been shown previously that non-melanoma skin cancers of renal transplant recipients and immunocompetent patients with skin cancer also frequently harbour potentially oncogenic HPV types. This study aimed to examine the integrity of the Rb gene in histologically confirmed squamous cell carcinomas (SCCs) from renal transplant recipients and immunocompetent patients with skin cancer. METHODS Loss of heterozygosity (LOH) at the Rb locus was examined in 13 histologically confirmed SCCs using the D13S153 microsatellite marker, which is located in exon 2 of the Rb gene. Loss of a second marker, D13S118, distal telomerically to the Rb gene at 13q14.3 was also analysed. RESULTS Of the 13 HPV associated SCCs examined 11 were informative (two SCCs were homozygous for both microsatellite markers). LOH at the D13S153 locus was found in four of the 10 informative SCCs and LOH at the D13S118 locus was found in five of the 11 informative cases. Overall, seven of the 11 informative cases showed LOH at one or other locus. This represents a high degree of chromosomal instability in these tumours. The expression of the Rb gene product in the 11 informative cases was analysed immunohistochemically. Expression of Rb was detected in 10 of the 11 SCCs examined. No correlation between the HPV status of the tumours and the expression of Rb was found. Although the only SCC not to express Rb also demonstrated LOH at the D13S153 locus, the remaining SCCs that had LOH at 13q14 were able to express RB: CONCLUSION Another tumour suppressor gene located at 13q14 might be responsible for the genesis of these tumours.