This paper describes an innovative method developed by the authors to support basic decisions concerning the structural restoration of a large historical panel painting which had been damaged by inappropriate attachment to a wall and ongoing exposure to severe changes in environmental humidity. The Lapidazione di Santo Stefano is a large panel (2.78 × 3.92 m2) painted by Giorgio Vasari in 1571 and has been housed since then in the Church of Santo Stefano dei Cavalieri in Pisa (Italy). Its wooden support is made of large horizontal planks glued together along their edges and stiffened by vertical, dovetailed crossbeams. The panel was tightly fastened to a church wall with several rigid bolts; due to the moisture cycling produced by rainwater leakage and a subsequent “compression set”, it had developed severe tension stresses perpendicular to the grain, resulting in cracks affecting both the wood and the paint layers. To decide how to carry out the structural restoration of the panel, it was necessary to know whether slippage could occur between the panel and crossbeams during seasonal variations in environmental humidity. Without slippage, tensile stresses would be generated in the wood and could produce further cracks and damage the paint layers. An in situ monitoring method for assessing the possibility of slippage was developed and implemented. An analysis of data collected over a period of 6 months before the structural restoration confirmed that adequate slippage was possible; hence, the decision to fully repair the cracks was taken. Monitoring continued for a year after restoration and confirmed the previous findings. This paper describes the monitoring method, the equipment used, the results of its implementation and its value as a preventive conservation tool.