Provided is a mask blank substrate that can reduce the change in flatness of a main surface thereof before and after chucking to make very small the position offset caused by a photomask and that can significantly reduce the difference in tendency of substrate deformation before and after chucking between photomasks. In a mask blank substrate having two main surfaces and four end faces, a central point is set on the main surface, a first axis of symmetry that passes through the central point and that is parallel to one of the end faces and a second axis of symmetry that passes through the central point and that is perpendicular to the first axis of symmetry are respectively set, measurement points are set in the form of a grid with respect to the first axis of symmetry and the second axis of symmetry so as to measure heights of the main surface from a reference plane at the measurement points, respectively, differences each between measured height values at those measurement points located at positions that are axisymmetric with respect to the first axis of symmetry are calculated, and those differences corresponding to at least 95% of the total number of the calculated differences between the measured height values are within a predetermined value.