Xeroderma pigmentosum, trichothiodystrophy and Cockayne-syndrome are rare, autosomal recessive genodermatoses, which are clinically heterogeneous. Generally, the first signs and symptoms appear at an early age. Although all three syndromes show photosensitivity and an underlying defect in the repair of UV-induced DNA damage, only patients with xeroderma pigmentosum have an increased skin cancer risk. The fact that all three of these syndromes can be caused by mutations in the same gene further emphasizes the role of these syndromes as an important model system for the pathogenesis of skin tumors. Recent findings in the fields of DNA repair, regulation of transcription and immunology have not only further unraveled the underlying mechanisms of these diseases but also provided important insights into the pathogenesis of skin tumors. The clinical characteristics of xeroderma pigmentosum and related DNA repair deficiencies are reviewed with an attempt to point out direct connections between clinical signs and symptoms and their underlying mechanisms.