Hemorrhagic pneumonia can be a major cause of mortality in farmed mink in the fall. Hemorrhagic pneumonia in its classic form is caused by the bacterium Pseudomonas aeruginosa. However, in recent years, we have experienced outbreaks of this type of pneumonia in farmed mink associated with hemolytic Escherichia coli. The purpose of this study was to compare histological lesions of acute hemorrhagic pneumonia in mink associated with P. aeruginosa and E. coli including a description of tissue distribution of pathogens in an attempt to differentiate the two disease entities on histopathology. The study included material from 2006-2009 submitted for diagnostic investigation at the National Veterinary Institute in Denmark. Altogether 19 cases of hemorrhagic pneumonia with a pure lung culture of P. aeruginosa and 18 cases of hemorrhagic pneumonia with a pure lung culture of E. coli were examined. Formalin fixed paraffin embedded lung tissue obtained from the mink were examined by histology and fluorescence in situ hybridization. It was possible to detect a slight histological difference between hemorrhagic pneumonia caused by P. aeruginosa and E. coli, as P. aeruginosa was found mainly surrounding blood vessels and lining the alveoli while E. coli showed a more diffuse distribution in the lung tissue. Furthermore P. aeruginosa often elicited a very hemorrhagic response in the lung while infection with E. coli were associated with a higher frequency of lungs displaying alveolar edema and mild lymphoid cuffing.