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Following the indication of the World Health Organization, a national plan for the elimination of measles was approved in Italy and this included the improvement of the molecular surveillance of measles viruses and the interruption of indigenous transmission of the disease. Nevertheless, large outbreaks continue to occur in almost all regions of the country, including Sicily. Here we describe the epidemiology and molecular dynamics of measles viruses as a result of the measles surveillance activity carried out by the "Reference Laboratory for Measles and Rubella" in Sicily over a 5-year period. Biological samples of 259 suspected measles cases were tested for viral RNA detection and a total of 223 (86.1%) were classified as laboratory confirmed. The median age of confirmed measles cases was 21.0 years and about half of them were adults aged 19 years and older. Overall, one-third of the patients showed clinical complications and these latter were more common among adults than children (44.9% vs. 25.7%). The vast majority of measles cases were unvaccinated (94.2%, n = 210). The phylogenetic analysis of 221 measles virus nucleotide sequences revealed sporadic detections of genotypes D4 and H1, while endemic circulation of genotypes D8 and B3 was documented. Genotype D8 was associated with epidemics occurred between 2013 and 2016, whereas genotype B3 was more recently introduced into Sicily characterizing the current measles outbreak. The results of this study confirm the autochthonous co-circulation of viral variants belonging to different genotypes during the study period, and emphasizes the need of measles surveillance programmes in order to investigate the viral dynamics, the pathways of disease transmission, and to eventually adapt the development of successfull vaccine formulations.