Human infections caused by Salmonella enterica serovar Napoli are relatively uncommon in Europe. Napoli was ranked 22nd in the Enter-net Salmonella database for 2006 with 295 cases (0.28%) of the 105,635 from 29 European countries. For the 18 countries that provided data for all the years 2000-2006, the number of cases rose from 122 out of 116,915 (0.10%) in 2000 to 293 out of 80,318 (0.36%) in 2006-an increase of 140.2%. Over 87% of cases came from three countries, France, Italy, and Switzerland. The epidemiology of the human cases showed an increased frequency in those aged under 5 or over 64, and both sexes were equally represented. Napoli isolates were also reported from nonhuman sources, mainly environmental samples and poultry. Strains compared by pulsed-field gel electrophoresis exhibited high levels of diversity between human, animal, and environmental sources. No single factor has been recognized as causing this rise, hence no public health interventions can be made or advice given to ensure that it does not persist. A 140% rise in 7 years indicates that the public health problem will continue, and further multidisciplinary investigations are needed to solve this enigma.