Salmonella enterica subsp. enterica serovar Dublin ( Salmonella Dublin) is a host-adapted bacterium that causes high morbidity and mortality in dairy cattle worldwide. A retrospective search of archives at the New York Animal Health Diagnostic Center revealed 57 culture-confirmed Salmonella Dublin cases from New York and Pennsylvania in which detailed histology of multiple tissues was available. Tissues routinely submitted by referring veterinarians for histologic evaluation included sections of heart, lungs, liver, spleen, and lymph nodes. Of the 57 S almonella Dublin-positive cases, all were Holstein breed, 53 were female (93%), and 49 (86%) were <6 mo of age. Specifically, in calves <6 mo of age, >90% (45 of 49) of lungs, 90% (28 of 31) of livers, 50% (11 of 22) of spleens, and 62% (18 of 29) of lymph nodes examined had moderate-to-severe inflammation with or without necrosis. Inconstant lesions were seen in 48% (10 of 21) of hearts examined, and consisted of variable inflammatory infiltrates and rare areas of necrosis. We propose a histopathology case definition of Salmonella Dublin in <6-mo-old Holstein cattle that includes a combination of pulmonary alveolar capillary neutrophilia with or without hepatocellular necrosis and paratyphoid granulomas, splenitis, and lymphadenitis. These findings will assist in the development of improved protocols for the diagnosis of infectious diseases of dairy cattle.