During computed tomography (CT), the appearance of disease involving the pulmonary acinus may be described using terms such as atelectasis, ground-glass opacity, or consolidation. These CT signs, however, have not been correlated with histologic findings in canine pulmonary disease. To facilitate interpretation of lung diseases by CT signs, our goals were to review the morphologic organization of the lung and evaluate the medical records of four dogs with different types of pulmonary acinar disease. Anatomic review focused on understanding the pulmonary acinus and the secondary pulmonary lobule; the secondary pulmonary lobule is a fundamental unit for interpretation in people. All dogs had similar CT findings of fully expanded lungs with increased attenuation and partial-to-complete obscuring of the pulmonary blood vessels. Histologic findings varied between dogs and included partial-to-complete filling of airspaces with cells or fluid, interstitial thickening, increased capillary blood volume, or a combination of these findings. Final diagnoses were hemorrhagic pneumonia, bronchiolar carcinoma, metastatic mammary adenocarcinoma, and pulmonary edema. In summary, the morphologic organization of the lungs is complex and has implications for diagnostic interpretation needing further evaluation in dogs. In this study, increased lung attenuation during CT due to disease localized to the pulmonary acini was due to the displacement of air from the lungs and not to the microscopic distribution of lesions within the pulmonary acinus. Imaging descriptors that classify diseases according to structures larger than the pulmonary acini, for example, regions of the secondary pulmonary lobule or larger, may be appropriate for dogs.