We examine whether F-term supersymmetric hybrid inflation can in a natural way be embedded within the minimal SO(10) model. We show that none of the singlets of the Standard Model symmetries in the minimal set of SO(10) representations can satisfy the conditions which are necessary for a scalar field to play the rôle of the inflaton. As a consequence, one has to introduce an extra scalar field, which, however, may spoil the naturalness of inflation within the context of SO(10). Nevertheless, if we add an extra scalar field, we are then able to construct a model that can accommodate flat directions, while it preserves the stability of the inflationary valley.