Previous karyotypic studies have indicated a possible series of non-random chromosomal events involved in progression of melanoma. We sought t o verify and augment this model of melanocyte tumorigenesis by studying allelic deletions of markers mapping t o these regions in 30 matched pairs of melanoma and constitutional DNA samples. Polymorphic loci on chromosomes I, 7, 10, I I, 17. and 2 I were analyzed and data combined with those previously obtained for chromosome arms 6q and 9p in the same series of tumours. The most frequent and earliest deletions were found on 9p (57%) and IOq (32%). With the exception of one case, no sample had loss of markers on another chromosome without concomitant loss of markers on 9p or I Oq. Losses on 6q were also a frequent (3 I %) and early event whereas losses of loci on distal I p (22%) or I I q (26%) occurred only in metastatic melanomas. A "background" rate (0-17%) of allele loss was seen on chromosomes 7, 17, and 2 I. These data strongly support the previous model based on karyotypic findings in rnelanocytic lesions. However, we have been able to further augment that model by delimiting the regions of loss on I Oq. t o that distal t o D I OS254, and on I p. t o between D I S243 and D I S 160. Genes Chrornosorn Cancer /2:/34-141 (1995). 0 I995 Wiley-Liss, Inc.