One hundred and fifty dogs with histopathologically confirmed intestinal disease were evaluated retrospectively. Sixty-one dogs had enteritis and 89 dogs had intestinal neoplasia. Ultrasonographic findings including the thickness and distribution of the intestinal lesion, the integrity of intestinal wall layering, regional lymph node thickness, the location of the intestinal segment involved, and regional motility were evaluated. Dogs with intestinal tumor had wall thickness (1.5 cm) significantly greater than dogs with NSE lesions (0.6 cm; p < 0.001). Ninety-nine percent of dogs with intestinal tumor had loss of wall layering while 88% of dogs with NSE had normal or altered wall layering (p < 0.001). Dogs with NSE were significantly more likely to have diffuse lesion (72%) than dogs with intestinal tumor (2%; p < 0.001). Lymph node median thickness in 24/61 dogs with NSE was 1.00 cm. The median thickness of the lymph nodes in 56/89 dogs with intestinal tumors was 1.9 cm. A multivariate analysis showed that loss of wall layering alone was an excellent predictive factor in differentiating intestinal tumor from NSE. In our population, dogs with loss of intestinal wall layering were 50.9 times more likely to have a tumor than enteritis.