An algorithm to locate the four modified Talairach cortical landmarks (A, P, L, and R) based on knowledge is proposed. Knowledge is employed to select the axial plane (the AP plane) passing through the anterior and posterior commissures, determination of optimum thresholds, segmentation, and refinement of the AP plane. The algorithm has been validated against 38 T1-weighted datasets from public resources. It takes less than 1 second on Pentium 4 (2.6 GHz) to extract the 4 landmarks. The average landmark location error is below 1 mm. The algorithm is robust and accurate as the factors influencing the determination of cortical landmarks like noise, gray level inhomogeneity, partial volume effect, and connection between the cortex and the sagittal sinus/meninges/skull are carefully compensated. A low computational cost is attributed to simple operations like thresholding, seeding, simple morphological operations and distance transform.