Patients with a family history of melanoma are at increased risk of this tumor. 
Those family members who also have the atypical mole syndrome are commonly 
targeted for screening in the belief that they are more likely to be mutant gene 
carriers. We have correlated the atypical mole syndrome phenotype and gene 
carrier status in five families with germline CDKN2A mutations and shown that 
family members with the atypical mole syndrome were three times more likely to 
be mutant gene carriers than their relatives who did not have the atypical mole 
syndrome (odds ratio 3.4; confidence interval 1.0-11. 1), supporting the view 
that CDKN2A is nevogenic. Individual characteristics which best predicted mutant 
gene carrier status were: nevi on the buttocks (odds ratio 4.4; confidence 
interval 1. 6-12.4), nevi on the feet (odds ratio 4.2; confidence interval 1. 
4-12.5), total nevus number being at least 100 (nevi > or = 2 mm in diameter) 
(odds ratio 3.4; confidence interval 1.0-11.1) and two or more clinically 
atypical nevi (odds ratio 3.1; confidence interval 1. 1-9.0). Gene carriers were 
also significantly more likely to have noticeable freckling and possibly also 
Fitzpatrick skin types 1-3. The overlap between gene carriers and nongene 
carriers was, however, marked: the atypical mole syndrome did not clearly 
differentiate mutant gene carriers from those with a normal gene. This study is 
of significance to clinicians as the clinical practice of using the atypical 
mole syndrome to identify particular family members for surveillance is shown to 
be inappropriate. Until formal gene testing is available, all members of 
families with an excessive number of melanoma cases should be treated as 
potential mutation carriers at increased risk of melanoma.