The most common human cancers are malignant neoplasms of the skin(1,2). Inc
idence of cutaneous melanoma is rising especially steeply, with minimal pro
gress in non-surgical treatment of advanced disease(3,4). Despite significa
nt effort to identify independent predictors of melanoma outcome, no accept
ed histopathological, molecular or immunohistochemical marker defines subse
ts of this neoplasm(2,3). Accordingly, though melanoma is thought to presen
t with different 'taxonomic' forms, these are considered part of a continuo
us spectrum rather than discrete entities(2). Here we report the discovery
of a subset of melanomas identified by mathematical analysis of gene expres
sion in a series of samples. Remarkably, many genes underlying the classifi
cation of this subset are differentially regulated in invasive melanomas th
at form primitive tubular networks in vitro, a feature of some highly aggre
ssive metastatic melanomas(5). Global transcript analysis can identify unre
cognized subtypes of cutaneous melanoma and predict experimentally verifiab
le phenotypic characteristics that may be of importance to disease progress
ion.