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Cankers and diebacks of European hop hornbeam (Ostrya carpinifolia) have been observed in the Italian Alps since 2001. In 2013, and 2014, field and laboratory investigations were performed in the provinces of Trento, Padua and Verona (northern Italy) to assess the presence and spread of disease affecting O. carpinifolia. Environmental and dendrometric data were recorded and analyzed, and samples were collected for the laboratory assays. Disease was observed in 106 of the 270 plots surveyed. In the majority of these, there were a small number of infections, but in some areas, severe attacks and multiple infections were recorded. Symptoms of decline, undoubtedly connected to cankers spreading across small surfaces, were observed in 31 plots. The presence of disease was positively correlated with sites predisposed to drought and correlated with lower altitudes. The fungus Botryosphaeria dothidea was found to be the primary agent involved in the disease, although Dothiorella parva was also isolated from the same infected tissues. However, both fungi were also obtained from healthy tissues, confirming their role as endophytes and/or latent pathogens. In inoculation tests, both species proved to be weakly pathogenic, but under laboratory conditions, they differed in their growth behaviors in relation to temperature. The annual growth of natural infection in the field is greater with higher autumn temperatures. The results indicate that the disease affecting O. carpinifolia occurred as a consequence of drought-related factors and high temperatures, and under changing climatic conditions, the disease is spreading in the surveyed areas of northeastern Italy. This study confirms field observations that revealed a higher incidence of new diseases in forests as a result of new climatic conditions with frequent extreme phenomena.