Non-melanoma skin cancer, i.e. basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most frequent tumors and their number is still increasing worldwide. Furthermore, immunosuppression in organ transplant patients strongly contributes to the increase in skin cancer incidence--being 65-250 times more frequent than in the general population. Often these patients suffer from a second and third lesion and the severity of these tumors is linked to their number. SCCs in transplant recipients also appear to be more aggressive. They tend to grow rapidly, show a higher rate of local recurrences and metastasize in 5-8% of the patients (all reviewed in Ref. 2). This largely differs from BCCs which are more frequent in the general population--at a ratio of 4:1 as compared with SCCs--but the number is only increased by a factor of 10 in transplant recipients. This may suggest that 'dormant' SCC precursor cells/lesions are present at a high frequency in the population but they are well controlled by the immune system. BCC, on the other hand, may be less dependent on immune surveillance thereby underlining its different etiology. While for BCC development the genetic hallmark is abrogation of the ptch-sonic hedgehog pathway, little is known about the causal alterations of SCCs. However, the complexity of the genetic alterations (numerical and structural aberration profiles) in SCCs argues for several levels of genomic instability involved in the generation and progression of skin cancer.