We juxtapose two patients—one with type 2 diabetes and one with systemic sclerosis (SSc)—who both exhibited severe hand joint restriction. Despite similar clinical findings, MRI revealed inflammatory tenosynovitis in SSc versus non-inflammatory fibrotic changes in diabetes. This comparison of clinical similarities and imaging differences highlights how a shared phenotype—the “prayer sign”—can arise from divergent mechanisms, and also suggest its potential use as a visible biomarker of systemic fibrosis with disease-specific implications.