The aim of this study was to identify magnetic resonance (MR) signs that aid differentiation of neoplastic vs. non-neoplastic brain diseases in dogs and cats. MR images of 36 dogs and 13 cats with histologic diagnosis of intracranial disease were reviewed retrospectively. Diagnoses included 30 primary and three metastatic brain tumors, 11 infectious/inflammatory lesions, three vascular, one degenerative disease, and one developmental malformation. Upon univariate analysis of 21 MR signs, there were seven that had a significant association with neoplasia: single lesion (P=0.004), shape (P=0.015), mass effect (P=0.002), dural contact (P=0.04), dural tail (P=0.005), lesions affecting adjacent bone (P=0.008), and contrast enhancement (P=0.025). Increasing age was also found to be associated with neoplasia (P=0.0001). MR signs of non-neoplastic brain diseases in dogs and cats were more variable than those of brain neoplasia.