Sunlight (ultraviolet radiation) has been identified as the major environmental risk factor for the development of cutaneous malignant melanoma and dysplastic naevi. This is, however, not sufficient to explain all melanoma cases. In recent years much emphasis has been given to genetic susceptibility to melanoma. A biomarker of susceptibility to environmentally related cancer is mutagen sensitivity. This is measured as the number of chromatid breaks in lymphocytes which are exposed to bleomycin in the G2 phase of the cell cycle. It has been described that patients with common melanoma show an increased mutagen sensitivity compared with controls. In the present study mutagen sensitivity was measured in 10 dysplastic naevus syndrome patients and compared with that in 11 patients with common melanoma. We found similar results for common melanoma patients as have been reported earlier: a relatively high mean breaks per cell value (0.93 ± 0.31). In contrast, melanoma patients with dysplastic naevi showed a significantly (P<0.01) lower mutagen sensitivity value (0.46 ± 0.34). This phenomenon was even more pronounced when only hereditary dysplastic naevi patients (one or more family members with dysplastic naevi) were considered (n=5; 0.24 ± 0.05). These results suggest a difference in the initiation of the carcinogenic process in melanoma with a dysplastic naevus as a precursor and melanoma without dysplastic naevi.