Homocysteine (Hcy) is a sulfur-containing α-amino acid that differs by one methylene (CH2) subunit from homologous cysteine (Cys). Elevated levels of Hcy are diagnostic markers of cardiovascular disease and other medical conditions. We present a new CuII-salicylidene glycinato complex 1 for the selective fluorometric detection of Hcy in water. In the presence of this analyte, the non-fluorescent copper-complex demetallates and disassembles into its building blocks. This process liberates a 3-chloro-5-sulfosalicylaldehyde signaling unit and is accompanied by a 51-fold turn-on fluorescence at 485 nm (λex=350 nm). Out of twenty proteinogenic amino acids, only histidine (12-fold turn-on fluorescence) and Cys (8-fold turn-on fluorescence) trigger some disassembly of probe 1. In comparison with important pioneering work on the detection of biothiols, this study strikingly demonstrates that structural modifications of chelate core structures steer substrate selectivity of metal-based probes. Importantly, probe 1 has proven suitable for the detection of Hcy in artificial urine.