Objective: Genetic changes during tumorigenesis are usually acquired sequentially. However, a recent study showed that in 2-3 % of all cancers a single catastrophic event, termed chromothripsis, can lead to massive genomic rearrangements confined to one or a few chromosomes. Method: In order to explore whether the degree of genomic instability and chromothripsis would influence prognosis in cancer, we applied high-resolution array comparative genomic hybridization to 20 malignant melanomas (MM) that were, despite comparable conventional clinical and pathological parameters, defined by a profoundly different clinical course. Results: We observed a striking association between both number and structure of chromosomal aberrations and outcome. MM associated with good prognosis showed only few chromosomal imbalances (average 1.6 alterations per case), predominantly presented as whole chromosome or chromosome arm gains and losses. MM with poor prognosis harbored significantly more chromosomal aberrations (13.9 per case; p=0.008). These aberrations were mostly focal events, which culminated in two cases in a pattern consistent with chromothripsis. Conclusion: Here, we describe for the first time the phenomenon of chromothripsis in primary MM and reveal a link between focal copy number alterations and chromothripsis with poor outcome in MM patients (p=0.0002), providing a genetic approach to predict outcome in histopathologically indistinguishable MM.