Oncogenic FGFR3 mutants R248C and S249C remain monomeric as long as they remain inside the cell in the endoplasmic reticulum and other intracellular compartments. Upon migration to the cell surface and exposure to the oxidative extracellular environment, disulfide-linked activated dimers of FGFR3 are formed, resulting in tyrosine phosphorylation and triggering of intracellular signaling pathways that result in bladder cell carcinoma proliferation (A). In their study in this issue of the JCI, Qing et al. (7) report that binding of their anti-FGFR3 mAb (R3Mab) to D2 and D3 of the extracellular ligand-binding region of FGFR3 before intermolecular disulfide linkages are formed prevents formation of disulfide-linked FGFR3 dimers with constitutively stimulated tyrosine kinase activity, resulting in the inhibition of bladder cell carcinoma proliferation and of tumor formation (B). Cysteines of R248C or S249C FGFR3 are shown in magenta. The stimulated tyrosine kinase domain is shown in red.