The present paper describes the results of preliminary numerical investigations on the static response of the Pisa Cathedral dome. After recalling the main geometric characteristics and relevant construction aspects of the dome, the results of the static analyses performed on a finite element model of the dome are presented and discussed. The simulations are conducted via the NOSA-ITACA code developed by ISTI-CNR for nonlinear static and dynamic analyses of historic masonry buildings. Masonry is assumed to be a no-tension material, for which a nonlinear elastic constitutive law is adopted. The numerical analyses focus on stress distribution, crack formation, and evaluation of the thrust at the dome’s base. The system formed by the vault and the drum is first examined when subjected to its self-weight, comparing the results to those obtained by limit analysis methods. The effects of settlements of the drum on the stress field and fracture strains are then examined to provide possible explanations for the crack pattern visible in the structure before restoration work.