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To identify reproducible anatomical landmarks that would allow predicting the course of the pyramidal tract (PT) through centrum semiovale.A total of 20 normal volunteers (12 males, eight females) with a mean age of 34 years (range, 20–59 years) were scanned using a 1.5-Tesla clinical MR unit to assess the trajectory of the PT. Neuroanatomical characteristics of the PT passing through the centrum semiovale were assessed by two independent observers. Tractography data of 10 consecutive patients with brain tumor were used to test the precision of anatomy-based prediction of the tract location.On sagittal view, 95% of the PT depicted on tractography displayed a completely straight or primarily straight course through the supratentorial brain. In 98% of tracts, the bending point of the PT was identified ≤3 mm from the level of the anterior commissure-posterior commissure (AC-PC) plane. In 80% of PT, the intersection with the AC-PC plane occurred midway between the AC and the PC as seen on the sagittal view. Evaluation of the PT in 10 patients with brain tumor revealed that the anatomy-based prediction of PT on the contralesional hemisphere was not substantially deviated from the actual tractography depicted PT. PT on the lesional hemispheres, however, had deviations of various degrees.The course of the PT through supratentorial brain can be predicted based on easily identifiable landmarks. This anatomy-based prediction can be clinically applied for cases without substantial mass effect from a space occupying lesion.