The thermoelastic behavior of a crystal of Fe-rich holmquistite with crystal-chemical formula A(K0.01Na0.01)B(Li1.88Mg0.10Na0.02)C(Mg1.68Al1.88)TSi8.00O22W[(OH)1.97F0.03] was studied by single-crystal X-ray diffraction at temperatures up to 1023 K, where isothermal annealing in air for 160 h yielded the loss of 0.85 H apfu coupled with oxidation of M1Fe. A complex pattern of cation exchanges was deciphered by comparing structure refinements done before and after annealing. Li migration from the M4 to M3 site is responsible for nonlinearity of the c parameter around 600 K during the first annealing. Cooling of the partially deprotonated crystal to room temperature (RT) showed discontinuities in trends of the b and c parameters around 820–800 K, which cannot be ascribed to a phase transition and can be explained by a rearrangement of the structural units affecting the geometry of the M4 polyhedron. Such discontinuities have never been observed in amphiboles before and must be related to dimensional constraints deriving from the peculiar composition of this amphibole, which contains the smallest possible homovalent constituents, i.e., BLi, CAl, and TSi. The calculated thermo-elastic parameters are: Fe-rich holmquistite: αa = 1.36(2)×10–5; αb = 0.55(1)×10–5; αc = 1.5(1)×10–5 – 6.7(9)×10–9; αV = 3.5(3)×10–5 – 0.8(3)×10–8 (polynomial); 2.58(6)×10–5 (linear); partially deprotonated Fe-rich holmquistite: αa = 1.324(9)×10–5 (RT-1023 K); αb = 0.60(1)×10–5 (RT-773 K); αc = 0.68(2)×10–5 (RT-773 K); αV = 2.59(2)×10–5 (RT-773 K). Fe-rich holmquistite is much stiffer than all the previously studied orthorhombic Pnma and Pnmn amphiboles. The results of this work allow progress toward a general model that may explain how the amphibole structure responds to non-ambient conditions, and allows the release of water in diverse geological environments.