Fatty infiltration of the pancreas is generally a diffuse process; however, it may be unevenly distributed in the pancreas. Focal fatty infiltration of the pancreas is usually most prominent in the anterior aspect of the head of the pancreas and seen as a region of decreased attenuation on computed tomography and may simulate pancreatic neoplasm. We discuss and illustrate the various features of focal fatty infiltration of the pancreas on multidetector row helical computed tomography with multiplanar reformation images and show how this imaging modality helps to differentiate between focal fatty infiltration of the pancreas and actual pancreatic tumors.