Protein Z, a vitamin K-dependent plasma protein, has been detected for the first time in a renal calculus along with osteopontin and prothrombin. The renal calculus was obtained from a hyperuricemic patient. Following two-dimensional polyacrylamide gel electrophoresis, the calculus was analyzed with the use of liquid chromatography mass spectrometry (LC-MS). The spectrometer was equipped with a nanoelectrospray interface and an ion trap. Four peptides were determined from a protein in the calculus through LC-MS/MS analysis. Tandem mass spectrum database matching tools were used to identify the protein as protein Z. Authentic protein Z was also analyzed using the same method, and all four peptides determined in the calculus were similarly identified. Whereas protein Z has been reported to be one of the vitamin K-dependent calcium-binding proteins, its role has not been well established. The fact that protein Z exists in a renal calculus composed of calcium oxalate will be beneficial in any future investigations into its role in the body.